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Sun, Wai-yin Raymond, and 辛偉賢. "The antitumor and antiviral properties of gold (III) porphyrins and their related complexes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31245973.
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Meza, Benjamin. "The Effect of Cell Type on the Efficacy of CMV Antiviral Drugs." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1567.
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Until recently, all in vitro drug susceptibility assays of cytomegalovirus (CMV) were performed in clinically irrelevant fibroblast cells. This study sought to test if drug susceptibility was affected by cell type. MRC-5 embryonic lung fibroblasts and ARPE-19 retinal pigmented epithelial cells were infected with BADrUL131-Y4 epithelial/fibroblast tropic virus under serial concentrations of ganciclovir (GCV) or maribavir (MBV). Virus was quantified using plaque reduction, GFP fluorescence, and yield reduction. Both drugs performed less efficiently in ARPE-19 cells. A cell type effect was observed for both plaque reduction and yield reduction assays with implications for the treatment of CMV retinitis as well as other manifestations of CMV Disease that involve non-fibroblast cell types.
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Ismail-Cassim, Nazeem. "The effect of short chain fatty acids on picornavirus replication." Thesis, Rhodes University, 1993. http://hdl.handle.net/10962/d1004090.
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Picornavirus proteins VP1 to VP3 are exposed on the surface of the virus particle whereas VP4 is internal and modified at its amino terminus by the addition of myristic acid (Chow et al., 1987; Paul et al., 1987). Myristic acid occupies a position in the core of mature poliovirus particles; it has been suggested that it may be important for particle integrity or in the localization of the capsid protein precursor on the hydrophobic membranes during virion assembly (Chow et al., 1987). To determine the function of the amino-terminal myristylation of VP4 in picornaviruses, and to establish whether competition for the acylation site is a possible approach to antiviral chemotherapy, the effect of fatty acids on virus replication has been examined. Some fatty acids are able to enter picornavirus-infected cells and compete for the myristylation site on VP4. Unexpectedly, it was found that short chain fatty acids also inhibit an early event in the replication of bovine enterovirus (BEV) at concentrations which have no detectable effect on cellular macromolecular synthesis and cloning. These findings indicate that fatty acids inhibit cell-mediated uncoating. Short chain fatty acids inhibit the replication of bovine enterovirus but are almost ineffective against poliovirus type 1, coxsackievirus B5, encephalomyocarditis virus and human rhinovirus lB. Lauric acid binds to bovine enterovirus, thereby stabilizing the virus particle to heat degradation. Fatty acid-bound virions attach to susceptible cells but fail to undergo cell-mediated uncoating. The inhibitory effect is reversible with chloroform and may result from a hydrophobic interaction between the fatty acid and a specific site on the virus particie.
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Marin, Brianna. "Determining the antiviral effect of HSP70 inhibitor, KNK437, by a time-dependent analysis." Walsh University Honors Theses / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=walshhonors1555516450619539.
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McGraw, Thomas L. (Thomas Lee). "The Effect of N, N Bis (ethylene)-P (1-adamantyl) Phosphonic Diamide on Rous Sarcoma Virus." Thesis, North Texas State University, 1988. https://digital.library.unt.edu/ark:/67531/metadc501033/.
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The drug, N,N bis (ethylene)-P (1-adamantyl) phosphonic diamide inhibits focus formation of Rous Sarcoma Virus in tissue culture. Transformation of chick cells was inhibited when the drug was added to chick cells prior to infection. The drug did not inhibit the transformation of Normal Rat Kidney Cells infected with RSV, when the cells were grown at non-permissive temperatures and shifted to permissive temperatures upon addition of the drug. Nor did the drug revert cells transformed at permissive temperatures. These studies indicated that the inhibition of RSV is in the early stage of viral growth, possible penetration or uncoating.
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Isorce, Nathalie. "Du criblage de l’activité antivirale de divers interférons et cytokines pro-inflammatoires contre HBV, vers la description du mécanisme antiviral de l’interleukine-1β dépendant de NF-κB." Thesis, Lyon 1, 2015. http://www.theses.fr/2015LYO10130.
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Dans les patients infectés par HBV, les thérapies avec les analogues de nucléos(t)ides (NAs) ou l'interféron α (IFNα) restent inefficaces pour éradiquer l'infection, à cause d'une forme persistante d'HBV, appelée l'ADN circulaire covalent clos (ADNccc), organisé comme un mini-chromosome. Notre but a été de revisiter l'activité anti-HBV d'un panel de cytokines in vitro en utilisant des hépatocytes non transformés, afin d'identifier de nouvelles options immunothérapeutiques. Parmi toutes les molécules testées, l'IFNβ, l'IFNγ, les IFNλ, le TNFα, l'IL-6, l'IL-1β et le ténofovir (ce dernier utilisé comme contrôle positif) ont montré un effet suppresseur sur la réplication d'HBV aussi fort et parfois plus fort que l'IFNα. La cytokine ayant l'effet le plus élevé sur l'ADN total d'HBV (EC50 ≈ 25 pg/mL), sans cytotoxicité, était l'interleukine-1β (IL-1β), qui est naturellement produite par les cellules de Kupffer (KC), les macrophages du foie. De façon importante, les ARNs totaux d'HBV et l'antigène sécrété HBeAg, mais pas HBsAg, ni l'ADNccc, sont fortement diminués par l'IL-1β. Nous avons donc émis l'hypothèse selon laquelle des promoteurs viraux spécifiques su l'ADNccc pourraient être inhibés, même si l'ADNccc n'est pas dégradé. Ensuite, nous avons étudié le mécanisme de l'activité antivirale de l'IL-1β. Nous avons montré que tous les promoteurs d'HBV sembleraient être inhibés par l'IL-1β. En parallèle, nous avons vérifié que l'IL-1β pouvait activer le promoteur de NF-κB, dont la fonction de transcription a été confirmée. Grâce à cette étude, l'IL-1β a été montré comme ayant un effet antiviral très efficace contre HBV in vitro, par l'intermédiaire de la fixation de NF-κB sur l'ADNcccIn HBV-infected patients, therapies with nucleos(t)ide analogues (NAs) or interferon α (IFNα) remain ineffective in eradicating the infection, because of a persistent form of HBV DNA, namely the covalently closed circular DNA (cccDNA), which is organized as a minichromosome. Our aim was to revisit the anti-HBV activity of a panel of IFNs and pro-inflammatory cytokines in vitro using nontransformed cultured hepatocytes of HBV infection, to identify new immunotherapeutic options. Amongst all molecules tested, IFNβ, IFNγ, IFNλ, TNFα, IL-6, IL-1β and tenofovir showed a suppressive effect on HBV replication at least as strong as, but sometimes stronger than IFNα. The cytokine showing the highest effect on intracellular total HBV DNA without any cytotoxicity, was interleukin-1β (IL-1β), which is naturally produced by Kupffer cells (KC), representing the macrophages of the liver. Importantly, total HBV RNAs and secreted HBeAg, but nor HBsAg, neither cccDNA, were strongly decreased. Thus, we hypothesized that even if cccDNA was not degraded, specific viral promoters on cccDNA could be silenced. Then, we investigated the mechanism of IL-1β antiviral activity. We have shown that all HBV promoters were early inhibited by IL-1β. In the meantime, we have verified that IL-1β can induce nuclear Translocation and expression of NF-κB. We also checked NF-κB functionality. Thanks to this study, IL-1β has been found to have very potent antiviral effect against HBV in vitro, through the binding of NF-κB on cccDNA
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Latham, Sally. "Proteomics to investigate hepatitis C virus infection and the effect of antiviral liposomes on host cells." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.547603.
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Somasundaram, Balaji. "A surface plasmon resonance assay to determine the effect of influenza neuraminidase mutations on its affinity with antiviral drugs." Thesis, University of Canterbury. Chemical and Process Engineering, 2013. http://hdl.handle.net/10092/9183.
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The outbreak of pandemic influenza and its ability to spread rapidly makes it a severe threat to public health. Antiviral drugs such as oseltamivir (Roche’s Tamiflu™) and zanamivir (GlaxoSmithKline’s Relenza™) are neuraminidase (NA) inhibitors (NI), which bind more tightly to NA than its natural substrate, sialic acid. However, the virus can acquire resistance to antiviral drugs by developing single point mutations (such as H274Y) in the target protein. Thus in some cases the drugs may not be as effective as expected. The high level of inconsistency exhibited by fluorometric assays and the short half-life of the chemiluminescent assay for monitoring drug resistance lead to the need for a simple, label-free, reliable assay. To address this problem, this work focused on three main objectives: 1) to determine the binding affinities of two common anti-viral drugs (oseltamivir and zanamivir) against the influenza NA wild type and drug resistant mutants using bioinformatics software Schrodinger Suite™ 2010. 2) To develop a reliable label-free, real-time, surface plasmon resonance (SPR) assay to measure the binding affinity between influenza viral coat protein neuraminidase (wild type and mutant) and anti-viral drugs. 3) To develop an SPR inhibition assay to quantitatively compare the interactions of sialic acid, zanamivir and oseltamivir with the viral coat protein neuraminidase (wild type and mutant).
The entire docking process was carried out using Schrödinger Suite™ 2010. The 2009 pandemic H1N1 neuraminidase (PDB: 3NSS) was used throughout the docking studies as the wild type structure. Five mutants (H274Y, N294S, H274N, A346N and I222V) and three ligands (sialic acid, oseltamivir and zanamivir) were built using the maestro module. The grid-based ligand docking with energetics (GLIDE) module and induced fit docking (IFD) module were used for docking studies. The binding affinities, Gibbs free energy change (∆G) and molecular mechanics-generalized born energy/ solvent accessible area (MM-GB/SA) values for wild-type NA interactions show that both the antiviral drugs studied interact strongly with the wild-type protein. The ∆G values for all antiviral interactions with mutant NA forms were reduced in magnitude, thereby indicating that they are less favourable than interactions with the wild-type protein. A similar trend was observed with MM-GB/SA results. Amongst all of the computed values, MM-GB/SA was the closest to the experimental data. In several cases, the interactions between the anti-viral drugs and NA mutants were markedly less favourable than those between sialic acid and the same mutants, indicating that these mutations could confer anti-viral resistance.
Influenza NA wild-type and H274Y mutant were expressed in baculovirus expression system (BVES) in insect cells. The expressed proteins were partially purified using the standard purification techniques of anion exchange and size exclusion chromatography (SEC). A fluorometric activity assay was performed on the recombinant proteins. Both the wild type and the mutant showed similar level of activities. In addition, the recombinant NAs were used in an inhibition assay. Oseltamivir was found to be sensitive to wild type protein (IC50 = 0.59 nM) and resistant to the H274Y mutant protein (IC50 = 349.43 nM). On the other hand, zanamivir was sensitive to both wild type (IC50 = 0.26 nM) and the H274Y mutant (IC50 = 0.44 nM). This indicated that zanamivir was a more potent inhibitor than oseltamivir. These findings were in good agreement with the literature.
An SPR assay for accurate monitoring of influenza antiviral drug resistance was developed. A spacer molecule (1, 6- hexanediamine) was site-specifically tethered to the inert 7-hydroxyl group of zanamivir. The tethered zanamivir was immobilized onto an SPR GLC chip to obtain a final immobilization response of 431 response units (RU). The reference subtracted binding responses obtained for NA wild-type and H274Y mutant were analysed using the ProteOn Manager™ Software tools. The SPR curves were fitted to a simple Langmuir 1:1 model with drift to obtain association rate constant (ka) and dissociation rate constants (kd). The relative binding values obtained from literature and the current SPR assay (1.9 and 1.7 respectively) suggested that the current SPR assay yielded similar results to the existing labelled enzymatic assay. In addition, an SPR inhibition assay was developed. The calculated IC50-spr values were compared and it was observed that oseltamivir was sensitive to wild type protein (IC50-spr = 7.7 nM) and resistant to the H274Y mutant protein (IC50-spr = 256 nM). On the other hand, zanamivir was sensitive to both wild type (IC50-spr = 2.16 nM) and the H274Y mutant (IC50-spr = 2.4 nM). Sialic acid was also found to be sensitive to both wild type (IC50-spr = 5.5 nM) and H274Y mutant (IC50-spr = 3.25 nM). In the cases studied, the viral proteins remained sensitive to sialic acid, consistent with retention of virulence of these mutant strains. It was concluded that zanamivir is a more potent inhibitor than oseltamivir for treating the H274Y mutant. Comparison of the SPR inhibition results with the docking results revealed a similar trend. The wild-type NA and H27Y mutant retained binding affinity for sialic acid and zanamivir. Oseltamivir showed a significant decrease in binding affinity for the H274Y mutant compared with the wild-type. This was because of the disruption of the salt bridge formation within NA that was vital for oseltamivir activity.
To my knowledge, this is the first SPR biosensor assay developed to monitor influenza antiviral drug resistance. There is a tremendous scope to extend this study to more mutants and new antiviral drugs. This could pave the way for a reliable SPR biosensor assay to replace low consistency labelled enzymatic assays.
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Gad, Hans Henrik. "Resistance of Chikungunya virus towards the antiviral effect of human 2',5'- oligoadenylate synthetase 3 involves the envelope E2 protein." Paris 7, 2012. http://www.theses.fr/2012PA077068.
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Le virus Chikungunya (CHIKV) est un alphavirus transmis par un moustique responsable d'une série d'épidémies en Afrique et en Asie durant la dernière décennie. Nous avons déjà montré que la 2',5'- oligoadenylate synthétase 3 (OAS3) induite par l'interféron possède une forte activité antivirale contre le CHIKV en empêchant l'accumulation d'ARN viral dans les cellules épithéliales humaines infectées. Dans ce travail, nous avons étudié la capacité du CHIKV a développer des stratégies d'échappement contre l'activité antivirale d'OASS. Par passage série d'un isolât clinique de CHIKV sur des cellules exprimant OAS3, nous avons identifié un variant qui montre une remarquable résistance envers OAS3. L'analyse de l'ARN génomique a permis d'identifier deux substitutions d'acides aminés : dans la protéine non structurale nsP2 et dans la glycoprotéine d'enveloppe E2. Grâce à un clone moléculaire de CHIKV exprimant la Renilla Luciférase, nous avons montré que seul le changement de Glu à Lys en position E2-166 est capable de restaurer la croissance virale dans les cellules humaines exprimant OAS3. L'étude de la croissance virale sur des myoblastes humains, qui sont associés à la pathogénèse du CHIKV, a montré que le CHIKV portant une lysine en position E2-166 se réplique plus efficacement que le virus sauvage. Cette efficacité de réplication accrue dans les myoblastes est associée à une forte phosphorylation de la PKR et d'elF2a suivie par une apoptose plus marquée des cellules. Nos résultats suggèrent que la substitution Glu166Lys dans la protéine E2 permets au CHIKV d'échapper à OAS3 en augmentant la réplication dans les cellules humaines plutôt qu'en agissant en tant que antagonisteChikungunya virus (CHIKV) is a mosquito-borne alphavirus that has reemerged within the last decade and caused a series of epidemics of unprecedented scale in Africa and Asia. We have previously reported that the interferon-inducible 2',5'-oligoadenylate synthetase 3 (OAS3) exerts potent antiviral activity against CHIKV in human epithelial cells by preventing accumulation of viral RIMA in infected cells. In this study, we investigated whether CHIKV may evolve strategies to circumvent the antiviral effect of OAS3. Through serial passage of a clinical isolate of CHIKV on OAS3-expressing cells, we identified a CHIKV variant which showed remarkable resistance towards OAS3. Analysis of its genomic RNA identified only two unique amino acid substitutions in the nonstructural nsP2 protein and the envelope E2 glycoprotein. Using a molecular clone of CHIKV expressing Renilla luciferase, we showed that only the change from Glu to Lys at position E2-166 was able to rescue viral growth in human cells expressing OAS3. Study of viral growth in human myoblasts, a host cell associated to the pathogenesis of Chikungunya disease, showed that CHIKV bearing Lys in E2-166 was more efficient at replicating in these cells when compared to wild-type virus. The greater efficiency of viral growth in myoblasts was associated with a robust phosphorylation of PKR and elF2a followed by more pronounced apoptotic cell death. Our data suggest that the Glu166Lys substitution in E2 enables CHIKV subversion of OAS3 by promoting viral growth in human cells rather than acting as an antagonist of PAS
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Amankwaah, Collins. "Incorporation of selected plant extracts into edible chitosan films and the effect on the antiviral, antibacterial and mechanical properties of the material." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366220367.
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Oladunni, Fatai S. "MECHANISMS OF TYPE-I IFN INHIBITION: EQUINE HERPESVIRUS-1 ESCAPE FROM THE ANTIVIRAL EFFECT OF TYPE-1 INTERFERON RESPONSE IN HOST CELL." UKnowledge, 2019. https://uknowledge.uky.edu/gluck_etds/43.
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Equine herpesvirus-1 (EHV-1) is one of the most important and prevalent viral pathogens of horses causing a major threat to the equine industry throughout most of the world. EHV-1 primarily causes respiratory disease but viral spread to distant organs enables the development of more severe sequelae; abortion and neurologic disease. In order to produce disease, EHV-1 has to overcome the innate barrier of the type-I interferon (IFN) system in host cells. However, the underlying mechanisms employed by EHV-1 to circumvent the type-I IFN response in host cells are not well understood. In this project study, using molecular techniques, we explored how EHV-1 is able to escape the type-I IFN response in host cells during infection. We also investigated whether EHV-4, a closely related but less pathogenic virus, has similar effects on type-I IFN as a clue to understanding how widespread IFN suppressive function is found among equine alphaherpesviruses.
Our data showed that inhibition of the type-I IFN response in host cells is not a function of neuropathogenicity of EHV-1 strains. However, a reduced type-I IFN response correlated with pathogenicity as EHV-4, unlike EHV-1, was unable to down-regulate the type-I IFN response in equine endothelial cells (EECs). Investigation of the mechanisms employed by EHV-1 to suppress type-I IFN revealed that the virus sequentially prevented outside-in signaling events that lead to type-I IFN production. Specifically, EHV-1 blocked the expression of Toll-like receptors (TLR) 3 and TLR4 at 6 hours post-infection (hpi) and 12 hpi. EHV-1 also prevented the transcription of IRF7 and IRF9 at different time-points during infection. The virus also perturbed the JAK-STAT signaling pathway by negatively regulating the cellular levels of TYK2 and phosphorylation-mediated activation of STAT2 molecules. Immunofluorescence data revealed that during infection, EHV-1 was able to sequester STAT2 molecules from nuclear translocation. This may be a limiting step preventing the formation of interferon- stimulated gene factor 3 (ISGF3) whose nuclear translocation is required to transactivate interferon-stimulated genes (ISGs) including IRF7.
Further investigation showed that unlike EHV-1, EHV-4 only interfered with phosphorylation-mediated activated STAT1 and STAT2 molecules at 3 and 6 hpi. EHV-4 was unable to block TLR3/4 and IRF7/9 mRNA expression at any time-point. Intriguingly, while viral late gene of EHV-1 mediates inhibition of STAT phosphorylation, our data showed that for EHV-4, a virus late gene did not mediate the inhibition of STAT phosphorylation. The findings from this study help illuminate how EHV-1 strategically interferes with limiting steps required for type-I IFN response in host cells to promote pathology. Our data also strengthen the hypothesis that the ability to shut off host factors required for type-I IFN production might be directly related to the degree of pathogenicity of the EHV subtypes.
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Eloy, Ygor Raphael Gomes. "CaracterizaÃÃo fÃsico-quÃmica e estrutural de polissacarÃdeos obtidos de folhas da planta Aloe barbadensis Miller e avaliaÃÃo de suas atividades antiviral e anti-hemorrÃgica." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8537.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorFundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico
Este trabalho teve como objetivos caracterizar fÃsico-quÃmica e estruturalmente polissacarÃdeos obtidos de folhas de Aloe barbadensis e avaliar suas atividades antiviral, anti-hemorrÃgica e prÃ-coagulante e possÃveis sinais de toxicidade. Foi realizada extraÃÃo aquosa de polissacarÃdeos totais (PT) de A. barbadensis, seguido de precipitaÃÃo por etanol e remoÃÃo dos contaminantes proteicos com TCA. A cromatografia em DEAE-celulose foi eficiente no fracionamento dos PT, onde foram obtidas as fraÃÃes PI e PII. A caracterizaÃÃo fÃsico-quÃmica mostrou que a fraÃÃo PI à composta por manose (78,4%), glucose (7,3%), galactose (2,1%), fucose (2,8%) e Ãcidos urÃnicos (10,0%), e isenta de grupos Ãster sulfato. Enquanto, a fraÃÃo PII à constituÃda por manose (39,2%), glucose (22,2%), galactose (26,3%), arabinose (3,8%), xilose (1,1%), Ãcidos urÃnicos (8,0%) e grupos Ãster sulfato (12,0%). Na revelaÃÃo das bandas polissacarÃdicas da fraÃÃo PII, obtidas por PAGE e gel de agarose corados com stainsall foi constatado a presenÃa de duas bandas que apresentaram diferentes coloraÃÃes, roxa e ciana, correspondentes a presenÃa de grupos sulfato e carboxilados, respectivamente. Na anÃlise estrutural das fraÃÃes PI e PII, por espectroscopia no IR, foi demonstrado que a fraÃÃo PI apresenta unidades monossacarÃdicas de Ã-manose O-acetiladas (812,2 e 960 onda.cm-1) e Ãcidos urÃnicos neutros (1738 onda.cm-1) em sua estrutura. Diferentemente, a fraÃÃo PII, mostrou-se ser constituÃda por unidades monossacarÃdicas de manose (1014,7 onda.cm-1), galactose (1078,2 onda.cm-1), Ãcidos urÃnicos carregados negativamente (1635 onda.cm-1) e Ãster sulfato (1329,5 e 1260,9 onda.cm-1). Na avaliaÃÃo estrutural da fraÃÃo PII por RMN foi comprovado à presenÃa do grupo Ãster sulfato. Em relaÃÃo Ãs atividades biolÃgicas, o teste de citotoxicidade mostrou que os PT e as fraÃÃes PI e PII nÃo apresentaram toxicidade para a maioria das cÃlulas testadas e nÃo foram eficientes na inibiÃÃo de vÃrus nÃo envelopados Ad-19 e Ad-41. No entanto, os PT e a fraÃÃo PI foram capazes de inibir a infecÃÃo causada por HSV-1 e HSV-2. Em ensaios com metapneumovÃrus (HMPV), a fraÃÃo PII apresentou atividade antiviral superior à ribavirina. Embora os PT e as fraÃÃes PI e PII nÃo terem apresentado atividade contra dengue vÃrus sorotipo 1 (DENV-1), os PT puderam inibir a hemorragia em ratos, diminuindo o tempo de sangramento e o tempo de protrombina. Os PT nÃo apresentaram toxicidade em camundongos, mas aumentaram o tamanho do baÃo e o nÃmero de plaquetas sanguÃneas. Pode ser concluÃdo que extratos foliares de A. barbadensis podem apresentar polissacarÃdeos neutros ou carregados negativamente por grupos carboxilados/sulfatados. Em adiÃÃo, alÃm de apresentar atividade inibitÃria contra os vÃrus HSV-1, HSV-2 e HMPV, podem tambÃm apresentar efeito anti-hemorrÃgico e prÃcoagulante, propriedades essas, importantes, visto que a complicaÃÃo de muitas viroses leva a quadros hemorrÃgicos. AlÃm disso, os PT de A. barbadensis nÃo apresentaram toxicidade expressiva, podendo ser utilizada como agente terapÃutico seguro e eficaz.
The aim of this study was to investigate the physicochemical and structural parameters of polysaccharides obtained from Aloe barbadensis leaves and to evaluate the antiviral and cytotoxic activities and procoagulant, anti-bleeding effects. In addition, toxicological analysis was carried out. The pulp was submitted to aqueous extraction (70 ÂC) and the total polysaccharides (PT) obtained by ethanol precipitation, TCA was used to remove the protein contamination. The fractionation of PT with DEAE-celulose resulted in two fractions (PI and PII). The physicochemical characterization showed that PI fraction presents mannose (78,4%), glucose (7,3%), galactose (2,1%), fucose (2,8%) and uronic acid (10,0%). Sulfate esters were not detected in PI fraction. On the other hand, PII fraction presents the monosaccharides mannose (39,2%), glucose (22,2%), galactose (26,3%), arabinose (3,8%), xylose (1,1%), uronic acids (8,0%) and sulfate esters groups (12,0%). The polysaccharidics of PII obtained by PAGE and agarose gel electrophoresis were revealed with toluidine blue and stainsall dye showing the presence of two different bands, one purple (indicative of sulfate) and another cyan (indicative of carboxilated groups). Structural analysis of PI and PII fractions by IR spectroscopy demonstrated that PI fraction is composed of residues of Ã-mannose O-acetylated (812.2 and 960 cm-1) and uronic acids (1738 cm-1). In contrast, the PII fraction is composed of mannose (1014.7 cm-1), galactose (1078.2 cm-1), negatively charged uronic acids (1635 cm-1) and sulfate ester (1329.5 and 1260.9 cm-1). These results corroborate with NMR analyses that suggest the presence of sulfate groups in PII structure. The cytotoxicity evaluation showed that PT and the fractions PI and PII did not show toxicity against most of tested cells and the same fractions were not effective against non-enveloped virus (Ad 19 and Ad 41) inhibition. However, the PT and PI fraction were able to inhibit the infection caused by HSV-1 and HSV-2. In addition, PII fraction presents antiviral activity against metapneumovirus. Although the PT and the fractions PI and PII did not show activity against dengue virus serotype 1 (DENV-1), PT could inhibit the bleeding effects in rats, reducing the bleeding and prothrombin time. The PT showed no toxicity in mice, but increased spleen size and number of blood platelets. In conclusion, A. barbadensis leaves contain neutral or negatively charged carboxylated/sulfated polysaccharides. In addition, besides having inhibitory activity against HSV-1, HSV-2 and HMPV, they can also anti-bleeding and procoagulant effect. Moreover, the PT of A. barbadensis showed no significant toxicity and can be used as a safe and effective therapeutic agent.
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Benedetti, Natália Augusto [UNESP]. "Avaliação da atividade antiviral dos compostos do esmalte de unha (acetato de etila e acetato de butila) no herpesvírus bovino tipo 5." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/137910.
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O Sistema de Vigilância Sanitária da Itália detectou 445 casos de hepatite B e 69 de hepatite C, relacionados aos tratamentos de beleza. Fato esse alarmante, pois, os cuidados com a aparência, têm levado a população a buscar os padrões de beleza estabelecidos pela mídia. Destacando-se que os salões de beleza no Brasil estão cada vez mais comuns com a atuação dos profissionais de manicure e pedicure. Entretanto, os produtos cosméticos necessitam de uma avaliação da qualidade sanitária, ou seja, testes que indicam a quantidade de micro-organismos viáveis em cada amostra. Pois, evidências mostram a sobrevivência dos Trichophytonrubrum, Trichopyton mentagrophytes, Candida albicans, Candida parapsilosis no esmalte de unha. Todavia, a composição e a fabricação do esmalte são pouco conhecidas, devido várias etapas estarem envolvidas na produção dos esmaltes de unhas comuns. Objetivo: Avaliar a ação dos solventes presentes no esmalte de unha, o acetato de etila e o acetato de butila, sobre o herpes vírus bovino tipo 5. Método: Realizou ensaios da atividade antiviral nas diferentes fases do ciclo replicativo com os solventes, acetato de etila e o acetato de butila. Resultados: No pré-tratamento, não houve replicação viral no acetato de etila a partir da diluição 10-6 e no acetato de butila 10-5 . No póstratamento não houve replicação viral no acetato de etila a partir da diluição 10-7 e no acetato de butila 10-5 e na inativação viral, tanto o acetato de etila como o butila, após 48 e 72 horas, todas as diluições apresentaram replicação viral, 10-1 a 10-10 . Discussão: Apesar de não identificar na literatura relatos específicos sobre solventes acetato de etila e acetato de butila na atividade antiviral, o presente estudo evidenciou que apesar de pouca diferença entre as diluições sequenciais desses solventes, houve replicação viral em diluições mais concentradas de vírus e de solventes. A limitação do estudo, com o uso do esmalte de unha, se deu pelo fato deste produto não ser diluído em meio de cultura para células em sua totalidade, além de conter substâncias muito voláteis que secam o produto rapidamente. Conclusão: Concluiu-se que houve replicação viral nas diferentes diluições, em maior concentração de solvente e maior número de vírus. Para diminuir o risco de contaminação cruzada da população pela disseminação de micro-organismos, mostra a necessidade dos órgãos fiscalizadores atuarem mais nesses estabelecimentos, educando e verificando a rotina do trabalho desses profissionais.
The Health Surveillance System in Italy detected 445 cases of hepatitis B and 69 hepatitis C related to beauty treatments. These alarming facts, for care of the appearance have led people to look for the beauty standards set by the media. If highlighting the beauty salons in Brazil is becoming more common with the activities of manicure and pedicure professionals. However, cosmetic products require a quality assessment of the health, is tests which indicate the amount of viable microorganisms in each sample. For evidence shows the survival of Trichophyton rubrum, Trichophyton mentagrophytes, Candida albicans, Candida parapsilosis in nail polish. However, the enamel composition and manufacturing are little known due several steps are involved in the production of common nail enamels. Objective: To evaluate the action of solvents present in nail enamel, ethyl acetate and butyl acetate, about herpesvirus bovine type 5. Method: The antiviral activity test performed at different stages of the replicative cycle of the solvents, ethyl acetate and butyl acetate. Results: In the pre-treatment, there was no viral replication in the ethyl acetate dilution from 10-6 to 10-5 in butyl acetate. In the post-treatment there was no viral replication in ethyl acetate from the dilution 10-7 and 10-5 butyl acetate and viral inactivation, both the ethyl acetate and the butyl after 48 and 72 hours, all dilutions they showed viral replication, 10-1 to 10-10 . Discussion: Although not identify the specific reports literature solvents ethyl acetate and butyl acetate in antiviral activity, this study showed that despite little difference between serial dilutions of these solvents, there viral replication in more concentrated dilutions of virus and solvents. A limitation of the study, using the nail polish, was due to the fact that this product is not be diluted in culture medium to cells in its entirety, and contain highly volatile substances that dry the product quickly. Conclusion: We conclude that there was viral replication in the different dilutions, higher solvent concentration and a higher number of viruses. To reduce the risk of cross-contamination of the population by the spread of micro-organisms, it shows the need for regulatory agencies act more in these establishments, educating and checking the routine work of these professionals.
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Benedetti, Natália Augusto. "Avaliação da atividade antiviral dos compostos do esmalte de unha (acetato de etila e acetato de butila) no herpesvírus bovino tipo 5." Botucatu, 2016. http://hdl.handle.net/11449/137910.
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Orientador: Ione CorrêaResumo: O Sistema de Vigilância Sanitária da Itália detectou 445 casos de hepatite B e 69 de hepatite C, relacionados aos tratamentos de beleza. Fato esse alarmante, pois, os cuidados com a aparência, têm levado a população a buscar os padrões de beleza estabelecidos pela mídia. Destacando-se que os salões de beleza no Brasil estão cada vez mais comuns com a atuação dos profissionais de manicure e pedicure. Entretanto, os produtos cosméticos necessitam de uma avaliação da qualidade sanitária, ou seja, testes que indicam a quantidade de micro-organismos viáveis em cada amostra. Pois, evidências mostram a sobrevivência dos Trichophytonrubrum, Trichopyton mentagrophytes, Candida albicans, Candida parapsilosis no esmalte de unha. Todavia, a composição e a fabricação do esmalte são pouco conhecidas, devido várias etapas estarem envolvidas na produção dos esmaltes de unhas comuns. Objetivo: Avaliar a ação dos solventes presentes no esmalte de unha, o acetato de etila e o acetato de butila, sobre o herpes vírus bovino tipo 5. Método: Realizou ensaios da atividade antiviral nas diferentes fases do ciclo replicativo com os solventes, acetato de etila e o acetato de butila. Resultados: No pré-tratamento, não houve replicação viral no acetato de etila a partir da diluição 10-6 e no acetato de butila 10-5 . No póstratamento não houve replicação viral no acetato de etila a partir da diluição 10-7 e no acetato de butila 10-5 e na inativação viral, tanto o acetato de etila como o butila, após 48 e ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The Health Surveillance System in Italy detected 445 cases of hepatitis B and 69 hepatitis C related to beauty treatments. These alarming facts, for care of the appearance have led people to look for the beauty standards set by the media. If highlighting the beauty salons in Brazil is becoming more common with the activities of manicure and pedicure professionals. However, cosmetic products require a quality assessment of the health, is tests which indicate the amount of viable microorganisms in each sample. For evidence shows the survival of Trichophyton rubrum, Trichophyton mentagrophytes, Candida albicans, Candida parapsilosis in nail polish. However, the enamel composition and manufacturing are little known due several steps are involved in the production of common nail enamels. Objective: To evaluate the action of solvents present in nail enamel, ethyl acetate and butyl acetate, about herpesvirus bovine type 5. Method: The antiviral activity test performed at different stages of the replicative cycle of the solvents, ethyl acetate and butyl acetate. Results: In the pre-treatment, there was no viral replication in the ethyl acetate dilution from 10-6 to 10-5 in butyl acetate. In the post-treatment there was no viral replication in ethyl acetate from the dilution 10-7 and 10-5 butyl acetate and viral inactivation, both the ethyl acetate and the butyl after 48 and 72 hours, all dilutions they showed viral replication, 10-1 to 10-10 . Discussion: Although not identify the sp... (Complete abstract click electronic access below)
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Garnier, Nathalie. "De l'étude du rôle des miARN dans la physiopathologie de l'infection par le SARS-CoV-2 à l'élaboration d'une application clinique." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. http://www.theses.fr/2024ULILS035.
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Le coronavirus 2 du syndrome respiratoire aigu sévère (severe acute respiratory syndrome-related coronavirus, SARS-CoV-2), de la famille Coronaviridae, est responsable de la maladie à coronavirus de 2019 (coronavirus disease 2019, COVID-19). Malgré la disponibilité de vaccins, en cause dans la fin de l’urgence sanitaire de la COVID-19, la circulation virale du SARS-CoV-2 subsiste ainsi que les recherches sur la compréhension de sa physiopathologie, notamment l’implication et le rôle des microARN (miARN) dans cette infection virale. Les miARN sont des petits ARN non codants régulant l’expression des gènes et connus pour leurs implications dans de nombreuses voies de régulation cellulaire. Récemment, ils se sont révélés l’être également dans l’infection par le SARS-CoV-2. Ces recherches permettraient une meilleure connaissance dans ce domaine et pourraient s’avérer utiles dans le développement de nouveaux diagnostics et de traitements cliniques contre cette infection virale ou d’autres infections de la même famille virale. Ainsi, dans ce projet de recherche, nous avons d’abord caractérisé les miARN cellulaires biomarqueurs de l’infection virale par le SARS-CoV-2 à partir de prélèvements nasopharyngés de patients, qui est le prélèvement recommandé pour le diagnostic de cette infection virale. Nos travaux ont identifié en particulier, des miARN associés à des formes sévères de la COVID-19. Ces derniers ciblent des gènes impliqués dans les infections virales et les réponses antivirales et anti-inflammatoires aux infections virales. Ces potentiels effets antiviraux et anti-inflammatoires des miARN sur l’infection virale par le SARS-CoV-2 n’ont pas pu être démontrés in vitro lors de cette étude. Par la suite, on s’est penché sur l’hypothèse de la dérégulation de la biogénèse des miARN par cette infection virale. On a trouvé aucune sous-expression des ARNm des gènes impliqués de la voie de biogénèse des miARN lors de l’infection par le SARS-CoV-2, que ce soit en ex vivo ou en in vitro. Pour finir, nous avons voulu développer un possible traitement clinique contre l’infection virale par le SARS-CoV-2 ou tout autre pathologie par la délivrance de miARN d’intérêt. Il s’agirait de développer des nanoparticules et des nanomatériaux couplés à des miARN ou autres ARN doubles brins messagers ou non, afin de permettre l’entrée de ces derniers au sein des cellules et rétablir ainsi l’expression basale des gènes impliqués dans l’infection viraleSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), a member of the Coronaviridae family, is responsible for coronavirus disease 2019 (COVID-19). Despite the availability of vaccines that helped end the COVID-19 health emergency, the viral circulation of SARS-CoV-2 remains, as well as research on the understanding of its pathophysiology, in particular the involvement and role of microRNAs (miRNAs) in this viral infection. miRNAs are small non-coding RNAs that regulate gene expression and are known to be involved in numerous cellular regulatory pathways. Recently, they have also been shown to be involved in SARS-CoV-2 infection. Such research would provide a better knowledge in this field and could be useful in the development of new diagnoses and clinical treatments against viral infection with SARS-CoV-2 or other infections of the same viral family. Thus, in this research project, we first characterized the cellular miRNA biomarkers of SARS-CoV-2 viral infection from patient nasopharyngeal swabs, which is the first diagnostic tool for this viral infection. In particular, our work has identified miRNAs associated with severe forms of COVID-19. These miRNA target genes involved in viral infections and antiviral and anti-inflammatory responses to viral infections. These potential antiviral and anti-inflammatory effects of miRNAs on SARS-CoV-2 viral infection could not be demonstrated in vitro in this study. Then, the hypothesis of deregulation of miRNA biogenesis by this viral infection was investigated. No under-expression of mRNAs of genes involved in the miRNA biogenesis pathway was found upon infection with SARS-CoV-2, either ex vivo or in vitro. Finally, based on a miRNA of clinical interest, we wanted to develop a possible clinical treatment against viral infection by SARS-CoV-2 or any other pathology through the delivery of miRNAs of interest, in this case antiviral. This would involve developing nanoparticles and nanomaterials coupled to miRNAs or other double-stranded messenger or non-messenger RNAs, to enable the latter to enter cells and thus restore basal expression of the genes involved in viral infection
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Desnues, Valérie. "Antiviraux et anticancéreux par voie percutanée." Paris 5, 1994. http://www.theses.fr/1994PA05P263.
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Hammonds, Timothy Robin. "Antiviral effects of podophyllotoxin derivatives." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335849.
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Kim, Dong Hyun. "Investigation of HIV anti-viral drug effect on HPV16 E6 expressing cervical carcinoma cells using advanced metabolomics methods." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-hiv-antiviral-drug-effect-on-hpv16-e6-expressing-cervical-carcinoma-cells-using-advanced-metabolomics-methods(d52b3b66-2a7b-4577-a334-b74bc12b27cc).html.
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Metabolomics approaches have recently been used to understand the complex molecular interactions of biological systems. One popular area in which these methods are being developed is to understand the biochemical changes during abiotic and biotic stresses; for example, how a cell may respond to a drug. Since metabolites are the end products of gene expression, these can be used to indicate the result of the activities and interaction of the cell or organism with its environment. The investigation of the level and compositional changes of metabolites against metabolic stresses such as chemotherapeutic treatment (drug exposure) are required to understand more fully abiotic perturbation to biological systems. The aim of this project was to understand the metabolic effect that the anti-viral drugs indinavir and lopinavir (currently used by HIV patients) have on HPV-related cervical cancer cell lines by measuring changes in metabolism using a wide range of analytical techniques; including Fourier transform infrared (FT-IR) and Raman spectroscopies, and gas and liquid chromatography-mass spectrometry (GC and LC-MS). The analyses and interpretation of the large volumes of complex multidimensional data generated by metabolomics approaches were performed with a combination of multivariate data analysis techniques such as principal components analysis (PCA) and canonical variates analysis (CVA), as well as univariate approaches such as N-Way analysis of variance (ANOVA). By combining biochemical imaging, metabolite fingerprinting and footprinting, and metabolite profiling, with multi- and uni-variate analyses, the actions and effects of the anti-viral drugs were investigated. FT-IR spectroscopy was initially used to generate global biochemical finger- and foot-prints, and Raman spectroscopy was employed to investigate intracellular distribution of metabolites, and other cellular species, as well as the localisation of drug molecules within cells. FT-IR spectroscopy ascertained that the intra- and extra-cellular metabolomes were being directly influenced in a fashion that correlated with increasing anti-viral dosing; these effects were phenotypic rather than measurements of the drug level. Raman imaging spectroscopy indicated that the indinavir but not lopinavir was being compartmentalised within the cell nucleus, but only in HPV early protein 6 (E6) expressing cells. This observation was further confirmed by fractionation of cell samples into nuclear and cytoplasmic fractions and assessing the indinavir concentrations via LC-MS. Finally, LC-MS and GC-MS metabolite profiling were employed to investigate changes in the intracellular metabolome in response to the anti-viral compounds across a range of physiologically relevant concentrations and in the presence and absence of the E6 oncoprotein. General effects of both anti-viral compounds included the regulation of metabolites such as glutathione, octenedionoic and octadecenoic acids, which may be involved in stress related responses, reduced levels of sugars and sugar-phosphates indicating a potential arrest of glycolysis, and reduced levels of malic acid indicating potential decreased flux into the TCA cycle; all indicating that central metabolism was being reduced. Finally, LC-MS based quantification indicated that in the presence of E6, lopinavir was actively removed from the cell, whereas the indinavir intracellular concentration increased concomitantly with the level of dosing. These investigations have revealed that metabolomics approaches are an apt tool for the study of anti-viral effects within cell cultures, but improvements need to be made with respect to the major limitation of metabolite identification.
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Woodhouse, Gillian Erica. "The effects of viral inactivation agents on the activities of monoclonal antibodies." Thesis, The University of Sydney, 1993. https://hdl.handle.net/2123/26592.
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The aim of this thesis was to determine whether or not two viral inactivation methods which had been developed for use with blood products, affected either antigen binding or secondary biological functions of two selected model antibody molecules. It was postulated that at least one of the viral inactivants, BPL, would affect the functional integrity of antibody molecules since it is reactive with proteins and has been used to block the complement-fixing properties of gamma-globulins.
As one of the most important functions of antibodies is opsonization, which occurs through binding of the F region to the Fe receptors in the cell membrane and binds complement, an in vitro model for this process such as hemolysis, serves ac a useful assay. Because haemagglutination and hemolysis serve as useful models for determining the functional integrity of antibodies in situ, these were the initial assays chosen to detect whether either of the two chemical viral inactivants, PL and TNBP, had a detrimental effect on the variable (antigen-binding) region or Fc region (effector function) of the two model monoclonal antibodies. However, the results from these assays were not clear cut and difficult to interpret due to both the inherent difficulty in reading the assays, i.e. the absence of an electronic component to provide sensitivity in measurement and the sensitivity of the antibody reaction to its physicochemical environment. The ELISA provides a useful comparison to haemagglutination and haemolysis assays as it overcomes these limitations. ELISAs can be used as a comparison but not a substitute for haemagglutination and haemolysis since the proteins are fixed onto a solid substrate so their mobility is restricted and the Fe is not assessed for its effector functions.
It is therefore proposed that a series of assays is required to determine the functionality of the variable and F regions of antibodies. In the future NMR will have a large part to play in the analysis of antibody purity but so far its use is limited to observing the conformation of variable domains. For the present, the assays chosen for this thesis were seen as the appropriate option to obtain data of greatest significance.
By ELISA it has been determined that the viral inactivation treatment using BPL with an IgM monoclonal antibody preparation resulted in a 25 % reduction in antigen-binding activity of the variable region, i.e. a 25 % reduction of antigen-antibody complex was detected. The results obtained from haemagglutination and haemolysis assays were less clear cut for reasons discussed previously. Initially, a reduction in titre for both haemagglutination and haemolysis was observed so that, as with the ELISA, a reduction in antigen binding activity followed treatment with BPL. Because an antigen-antibody complex has a greater affinity for an Fc receptor than an unbound antibody, the reduction in haemolytic activity does necessarily indicate a chemical modification of the Fc region. Subsequently, when the assays were repeated in the presence of 5 % BSA, a reduction in neither the haemagglutination nor the haemolytic titres were observed. It is conceivable that while the affinity constant and hence detectability was increased using BSA, the precision of the measurement was reduced to such a degree that the differences in avidity of the antibody molecules could not be detected.
No significant alteration in overall biological activity, as measured by ELISA, haemagglutination or haemolysis resulted when the same IgM monoclonal antibody preparation was subjected to the viral inactivation procedure using TNBP. No significant alteration in the antigen-binding activity, measured by haemagglutination resulted when a model human IgG1 monoclonal antibody preparation was subjected to the viral inactivation procedures using either TNBP or BPL; however, this assay was carried out in the presence of 5 % BSA and, as been concluded from the previous experiments, further assays may be required to detect an alteration.
It may be concluded that although the use of EPL as an viral inactivant is the only chemical treatment method available to inactivate all viruses for which it has been tested, it significantly reduces the antigen-binding ability of a mouse IgM molecule; also, it is likely that /LPL modifies the Fc region to reduce its functional integrity (115). Procedures such as filtration or lyophilisation have advantages in that they have been demonstrated to yield a safe product; however, filters available cannot remove very small viruses and the use of lyophilisation for inactivation has not been substantially investigated.
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Willig, Jennifer A. "Analysis of Antiviral and Chemoprotective Effects of Strawberry Anthocyanins." UKnowledge, 2013. http://uknowledge.uky.edu/animalsci_etds/28.
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This study investigated the antiviral, chemoprotective and proliferative effects of strawberry anthocyanins on herpes simplex virus type-1, cancerous cell lines HT-29 and AGS, and normal cell lines Hs 738.St/Int and CCD-18Co. Antiviral properties were measured by infecting vero cells from adult grivet (Cercopithecus aethiops) with herpes simplex virus type-1 (HSV-1) and treating with a concentration of 1.25-20 µg/mL of strawberry anthocyanins. Infectivity and replication were quantified for herpes simplex virus type-1 using the direct plaque assay and reporting PFU/mL. Strawberry anthocyanins (>20 µg/mL) inhibited the herpes simplex virus infectivity in vero cells by 100% (p<0.05). Strawberry anthocyanins at concentrations of 5, 10 and 20 μg/mL were reduced to 75.36, 57.98, and 31.46 percent of the control (100%) (p<0.05).
Chemoprotective and proliferative effects of strawberry anthocyanins were analyzed for the human cell lines AGS, Hs 738.St/Int, HT-29, and CCD-18Co at a concentration of 25-200 µg/mL and quantified using the sulforhodamine-B assay. Growth inhibition occurred at a level of ≥87% for treatment concentrations 100 and 200 µg/mL for the cancerous AGS and HT-29 cell lines (p<0.0001). Proliferation rates for the normal Hs 738.St/Int and CCD-18Co cell lines increased at all treatment concentrations of 25-200 μg/mL (p<0.0001); suggestingthat the observed proliferative activity may be associated with anthocyanin treatment.Strawberry anthocyanin treatment concentration worked in a dose dependent manner for the HSV-1 and the cancerous AGS and HT-29 cells. The caspase-3 assay was performed to demonstrate potential mechanism of action and confirmed thatanthocyanin treatments play a role in apoptosisby the up regulation of caspase-3.Significantdifferences were seen between the growth characteristics of cancerous cell linescompared to their equivalent normal cell lines (p<0.0001).
In summary, the antiviral findings suggest that strawberry anthocyanin extracts could be an effective topical treatment and/or prophylactic agent for oral herpetic infections (HSV-1). Also, the in vitro chemoprotective effect of strawberry anthocyanins found may be relevant to in vivo work in the future because when anthocyanins are consumed in the diet they come in direct contact with the gastrointestinal tract and may provide chemoprotection upon contact with the stomach and gastrointestinal tract’s epithelial cell layer.
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Meng, Alice Xianyue. "Effects of C- and N-terminal deletions on antiviral and ribosome-inactivating activities of pokeweed antiviral protein, PAP." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0018/MQ28734.pdf.
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Meers, Joanne. "The effects of antiviral agents on feline immunodeficiency virus infection." Thesis, Meers, Joanne (1994) The effects of antiviral agents on feline immunodeficiency virus infection. PhD thesis, Murdoch University, 1994. https://researchrepository.murdoch.edu.au/id/eprint/53284/.
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Feline immunodeficiency virus (FIV) is a recently discovered lentivirus with many structural and replicative similarities to human immunodeficiency virus (HIV), and has been suggested as a useful animal model for the evaluation of anti-HIV chemotherapy. The successful use of the model is dependent on the development of techniques to accurately measure the response to antiviral treatment in FIV-infected cats.
FIV was isolated by the co-cultivation of peripheral blood mononuclear cells (PBMC) from seropositive cats with PBMC of seronegative donor cats, or with MYA-1 cells (a feline T-lymphoblastoid cell line). Propagation of FIV isolates was unsuccessful in Crandell feline kidney cells, but was successful in PBMC cultures, primary feline thymocytes, and MYA-1 cells.
The biological characteristics of 3 West Australian isolates of FIV were compared. The isolates had similar properties to each other, and to other reported isolates of FIV, including similar cytopathic effect (CPE), electron microscopic appearance, magnesium-dependent reverse transcriptase (RT) activity, FIV p26 core antigen production and the nucleotide sequence of gag and pol genes.
Tetrazolium-based colourimetric assays were used to quantify the CPE of FIV by demonstrating the loss of cell viability in FIV-infected MYA-1 cell cultures. These assays were then used for the titration of FIV, to assess the cytotoxicity of antiviral agents in vitro, and to determine the protection provided by antiviral agents against the CPE of FIV. Five of 6 agents evaluated by these assays provided protection against CPE induced by 2 isolates of FIV. These agents consisted of 4 RT inhibitors (zidovudine, ddC, ddI, foscarnet) and one inhibitor of virus binding/entry (dextran sulphate). A novel agent, acemannan, provided no protection against the CPE of FIV. The inhibition by zidovudine of RT activity and FIV p26 antigen levels in culture supernatant was also demonstrated.
The titre of FIV in PBMC and plasma was determined in 18 experimentally-infected cats and 2 naturally-infected cats, by end-point dilution cultures. The proportion of PBMC containing provirus was determined by polymerase chain reaction (PCR) on serially diluted samples of PBMC from 10 cats. It was demonstrated that following inoculation with virus, the titre of FIV in PBMC increased rapidly to a relatively high level which was then maintained for up to 8 months. In most cats, approximately 1 in 200 PBMC contained virus by 4 weeks post inoculation (p.i.). The results from PCR generally correlated with those from virus isolation, suggesting that the proportion of FIV provirus that is replication defective may be comparatively low. The titre of FIV in plasma peaked at approximately 2 weeks p.i., and then in many cats, declined to undetectable levels. Virus was not isolated from plasma of 2 naturally-infected cats. In some cats, plasma virus titres did not decline by up to 32 weeks p.i., suggesting that there is a variation in the immune response, which enables some, but not all, cats to clear virus from plasma.
The effect of treatment with cyclosporine on the virus titre in cats experimentally infected with FIV was investigated. Treatment began 24 hrs p.i., and continued for 4 weeks. Cyclosporine treatment lowered plasma virus titres at 2 weeks p.i., but at 4 weeks p.i. the plasma virus titre of cyclosporine-treated cats was significantly higher than in untreated cats. This suggested that, initially, the suppression of T-cell activation resulted in the inhibition of viral expression and lower plasma virus titres. However, the broader immunosuppressive effect of treatment eventually dominated the former effect, resulting in an inability to control viral replication and/or clear virus from plasma. Cyclosporine treatment did not influence the titre of FIV in PBMC.
The studies on virus load, combined with the cyclosporine data, suggest that the immune response plays a major role in the control of plasma virus titres in lentiviral infections, but has little influence on the level of cell virus titres.
Treatment of infected cats with zidovudine resulted in significant effects on virus load. Two different dose rates of zidovudine, administered at different times p.i. and with different durations of treatment, were assessed. Zidovudine treatment, with either dose regime, did not prevent establishment of infection with FIV. However, the plasma virus titre of zidovudine- treated cats, using either dose regime, was significantly lower than in untreated cats on at least one sampling occasion. The PBMC virus titre of cats treated with the higher dose of zidovudine was significantly lower than untreated cats at two sampling times. Treatment with the lower dose of zidovudine did not significantly influence PBMC virus titre. This suggested that while the effect of zidovudine on the level of PBMC virus titre may predominantly be the result of the inhibition of viral RT, the effect of zidovudine on plasma virus titres may be the result not only of RT inhibition, but also the result of the suppression of T-cell activation by zidovudine.
This work established methods by which the effect of antiviral or immunomodulating agents on the titres of FIV in PBMC and plasma of infected cats can be investigated and has demonstrated that FIV infection can be used as an effective animal model for the evaluation of antiviral agents against HIV. It has also contributed to the broader investigation of the immunopathogenesis of lentiviral infections.
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Lambour, Jennifer. "Rôle des polynucléaires neutrophiles et du FcgRIV dans les effets vaccinaux induit par immunothérapie antivirale par anticorps monoclonaux." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT064/document.
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Les anticorps monoclonaux (AcM) sont désormais considérés comme une alternative thérapeutique crédible pour traiter les infections virales graves. Comprendre leurs multiples mécanismes d’action est donc crucial pour améliorer leur effet thérapeutique. En utilisant un modèle d’infection virale chez la souris (leucémie induite par le rétrovirus FrCasE), l’équipe a montré qu’une immunothérapie courte par un AcM neutralisant induisait une immunité antivirale protectrice sur le long-terme (effets « vaccinaux ») qui est dépendante du fragment Fc de l’AcM. Ainsi, des immuns complexes (IC) formés à partir de l’AcM thérapeutique et de déterminants viraux, induisent l’activation de cellules immunitaires, notamment les cellules dendritiques (DCs), via leur interaction avec les FcRs exprimés à la surface des cellules. Cependant, ces interactions IC-FcR peuvent également concerner d’autres cellules du système immunitaire outre que les DCs, telles que les macrophages, monocytes ou bien encore les neutrophiles, qui expriment elles aussi les FcRs à leur surface et ce de façon différentielle. Dans ce contexte, il est important d’identifier quels FcRs et quelles cellules les exprimant sont essentiels à l’induction des effets vaccinaux par les AcM. C’est pourquoi mes travaux thèse se sont focalisés sur l’étude du rôle des neutrophiles et des FcγRs dans la modulation de la réponse immune par les AcM. Cette étude repose sur le caractère Fc-dépendant de l’induction d’une réponse immune protectrice par les AcM ainsi que sur les propriétés immunomodulatrices des neutrophiles, qui ont été décrites dans différents contextes pathologiques mais jamais étudiées dans le cadre d’une immunothérapie antivirale par AcM. Pour cela, j’ai utilisé différentes approches in vitro, ex vivo et in vivo.En utilisant le modèle d’infection par FrCasE, il a été montré que les neutrophiles ainsi que le FcγRIV ont un rôle crucial dans l’induction des effets vaccinaux par les AcM, notamment via l’induction d’une réponse humorale antivirale endogène protectrice à très long-terme. De plus lors d’expériences in vitro, il a également été souligné que les neutrophiles sont plus efficacement activés par les IC comparé au virus seul et que différentes cytokines pro-inflammatoires et/ou immunomodulatrices (telles que le TNF et les intérferons de type I et II) potentialisent l’activation des neutrophiles induite par les IC. Mes travaux ont aussi mis en évidence que l’infection virale et l’immunothérapie modulent l’expression des FcRs, et notamment induisent la surexpression du FcRIV sur deux populations distinctes de neutrophiles (différentiées par le niveau d’expression du marqueur de surface Ly6G: Ly6Ghi et Ly6Gint) et sur les monocytes inflammatoires. Enfin, mes travaux montrent que l’immunothérapie par AcM module les profils de sécrétion chimiokinique et cytokinique de ces 3 types cellulaires surexprimant le FcRIV, bien que la nature des profils de sécrétion varie en fonction du type cellulaire et évolue au cours du temps. Ces résultats suggèrent que l’effet immunomodulateur des AcM repose sur l’activation de différents acteurs de la réponse immunitaire précoce, en induisant la sécrétion de chimiokines et de cytokines nécessaires à l’orchestration de la réponse immune. Ils suggèrent aussi une coopération entre ces différents acteurs dans la mise en place d’une immunité protectrice.Pour finir l’ensemble de mes travaux ont mis en évidence un rôle immunomodulateur clé du FcyRIV, ainsi que des différentes cellules l’exprimant, dans l’induction d’une réponse immune protectrice induite par des AcM antiviraux. Ces révélations pourraient avoir des conséquences importantes dans l'amélioration des immunothérapies à base d'AcMMonoclonal antibodies (mAbs) are now considered as a true therapeutic alternative for treating severe viral infections. Figure out their multiple mechanisms of action is therefore crucial to improve their therapeutic effect. Using a mouse model of viral infection (the FrCasE retrovirus-induced leukemia), the team showed that a short immunotherapy with a neutralizing mAb induces long-term protective antiviral immunity ("vaccine" effects) which is Fc-dependent. Notably, immune complexes (IC) formed with therapeutic mAbs and viral determinants induce the activation of immune cells, especially dendritic cells (DCs) via their interaction with FcγRs expressed on the cell’s surface. However, IC-FcγR interactions can involve different cells of the immune system in addition to DCs, such as macrophages, monocytes or neutrophils, which differentially express FcγRs. In this context, it is important to identify which FcγRs and which FcγR-expressing cells are crucial in the induction of vaccine effects induced by mAbs. It’s the reason why my thesis work has focused on the study of the role of neutrophils and FcγRs in the modulation of immune response by mAbs. This study is based on the Fc-dependent nature of the induction of a protective immune response by mAbs and the immunomodulatory properties of neutrophils, described in different pathological situations but never studied in an mAbs antiviral immunotherapy context. To this end, I used different approaches in vitro, ex vivo and in vivo.By using the FrCasE infection model, it has been shown that neutrophils as well as FcγRIV have a crucial role in the induction of vaccine effects by mAbs, notably via the induction of a long-term protective antiviral humoral response. Moreover the in vitro experiments, highlighted that neutrophils are more effectively activated by IC compared to virus alone and that different pro-inflammatory and/or immunomodulating cytokines (i.e.TNFα and type I and type II interferons) potentiate the activation of neutrophils induced by IC. My work also revealed that viral infection and immunotherapy modulate the expression of different FcγRs, and notably they induce the overexpression of FcγRIV on two distinct populations of neutrophils (differentiated by their expression levels of the Ly6G surface marker: Ly6Ghi and Ly6Gint) and inflammatory monocytes. Finally, my work shows that immunotherapy with Mab modulates the chemokinic and cytokinic secretion profiles of these 3 FcγRIV-over-expressing cell, although the nature of the secretion profiles differs according to the cell type and evolves over time. These results suggest that the immunomodulatory effect of mAbs is based on the activation of different actors of the early immune response by inducing the secretion of chemokines and cytokines necessary for the orchestration of the immune response. They also suggest a potential cooperation between these different actors in the establishment of protective immunity.Altogether, these results show a key immunomodulator role of FcγRIV as well as of different cells expressing it in the induction of a protective immune response by antiviral mAb. They might have important consequences for the improvement of Mab-based immunotherapies
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Sui, Hongyan, and 隋洪艷. "Studies on antiviral effects of siRNAs against H5N1 influenza A virus infection." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41508245.
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Sui, Hongyan. "Studies on antiviral effects of siRNAs against H5N1 influenza A virus infection." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41508245.
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Zhang, Ke, and 张科. "Evaluation of anti-human respiratory syncytial virus effects of short interfering RNAs and β-defensin-4." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/209570.
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The human respiratory syncytial virus (hRSV) infection is a global public health burden in children aged under 2 years and immunocompromised or elderly adults. The choice for prophylaxis and therapy of hRSV infection was constrained to Palivizumab and Ribavirin. Therefore, this study aimed to develop effective anti-hRSV infection agents, such as short interfering RNA (siRNA) and β-defensin-4 (β-D-4).
Since there still is no compatible animal model to evaluate antiviral effect of anti-hRSV agents, we first attempted to establish suitable animal model. A clinical isolate of hRSV (KI-RSV-W) was adapted in BALB/c mice by serial passages. Old male mice (age > 8 months) were used for establishment of hRSV infection model, because the more efficient viral infection in lungs of the old male mice than that old female mice and young mice (age < 3 weeks). After the virus was propagated in old male mice for 20 passages, a virus variant KI-RSV-P70-4 exhibited more efficient infection/replication in the mice. Its viral load was about 100-fold higher than that of wild type strain KI-RSV-W. The infection of KI-RSV-P70-4 also caused more severe histopathological changes in lung tissues. Although KI-RSV-P70-4 could not result in death of the infected mice, both viral load and pathological change in lungs may be good indicators for evaluating antiviral effect. The mouse model and adapted hRSV strain solidly laid the foundation for evaluation of anti-hRSV agents.
We then designed and evaluated anti-hRSV effect of siRNAs. A total of 25 siRNAs targeting 4 viral genes (M2-1, NS2, N and F) were designed and their anti-hRSV effect was assessed in vitro. The results showed that 6 siRNAs respectively targeting M2-1, N and F genes exhibited higher anti-hRSV effect than that of the positive control, whereas those targeting NS2 gene did not show significant antiviral effect. The 50% inhibitory concentrations (IC50) of three most potent siRNAs (M2-1-361, N889 and F-1143) were 0.51, 2.14 and 0.64 nM, respectively.
Antiviral activity of β-D-4 against hRSV infection was evaluated in vitro and in vivo. In vitro experiments showed supreme antiviral effect with IC50 around 3.4 μg/ml when the virus was pretreated with β-D-4, but no significant inhibitory effect was observed when the cells were pretreated with β-D-4 or β-D-4 was maintained in the culture medium after viral infection. These results indicated that the inhibitory effect of β-D-4 was associated with direct interaction with the virus itself and blocked virus entry of the cells. Furthermore, a single dose (13.6 μg) of β-D-4 intratracheal (i.t.) administration in old male mice after the viral infection resulted in about 0.7 log reduce of viral load in lung tissues, while inoculation of premixed β-D-4 and the virus caused about 3 logs decrease of viral load in lungs. These results have demonstrated that β-D-4 may be an effective anti-hRSV agent.
Taken together, old male BALB/c mice might be used to establish hRSV infection model. Three siRNAs and the β-D-4 were validated as the potent anti-hRSV agents, respectively.published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
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Lu, Lei, and 呂雷. "Effects of antiviral therapies on hepatitis B virus relicaptive intermediates in chronic hepatitis B." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42182359.
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Nußbaum, Benedikt Lukas [Verfasser]. "Effects of commonly used antiviral vaccines on human plasmacytoid dendritic cells / Benedikt Lukas Nußbaum." Ulm : Universität Ulm. Medizinische Fakultät, 2013. http://d-nb.info/1035700220/34.
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Lu, Lei. "Effects of antiviral therapies on hepatitis B virus relicaptive intermediates in chronic hepatitis B." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42182359.
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Cornacini, Milena Costa Menezes [UNESP]. "Efeito do uso do cogumelo Agaricus brasiliensis no estado nutricional, na frequência e intensidade dos efeitos adversos da terapia medicamentosa e na resposta bioquímica hepática em indivíduos com hepatite crônica pelo vírus C: estudo prospectivo, randomizado, duplo cego, placebo controlado." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/102636.
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Diversos estudos, indicam que o cogumelo Agaricus brasiliensis é benéfico em várias condições clínicas, como na hepatite C. Várias espécies de cogumelos comestíveis têm sido exploradas quanto ao seu potencial medicinal e muitos pacientes passam a buscar a solução para suas patologias nas terapias complementares. Avaliar os efeitos da suplementação do Agaricus brasiliensis sobre o estado nutricional, a frequência e a intensidade dos efeitos adversos da terapia antiviral e a resposta bioquímica hepática em indivíduos com hepatite C em tratamento com Interferon peguilado e Ribavirina. Foi realizado um ensaio clínico prospectivo controlado casualizado duplo cego no Serviço de Hepatites Virais do Hospital das Clínicas da Faculdade de Medicina de Botucatu-UNESP. Os indivíduos do estudo foram submetidos a um protocolo de suplementação com cogumelo ou placebo por 24 semanas, e foram distribuídos aleatoriamente nos seguintes grupos: Grupo tratado com placebo (5g/dia n=14) e Grupo tratado com cogumelo (5g/dian= 9).Todas as análises foram obtidas antes e após os tratamentos (placebo ou cogumelo). O estado nutricional (dados antropométricos, de composição corporal, da bioquímica nutricional e do consumo alimentar), foi semelhante entre os grupos. Houve melhora da lesão hepática em ambos os grupos, com redução de transaminases (TGO/AST e TGP/ALT, p<0,05), mostrando a eficácia do tratamento antiviral.O uso do cogumelo mostrou-se benéfico na redução da frequência e intensidade dos efeitos adversos da terapia medicamentosa (mialgia, disgeusia, cefaléia, redução do desejo sexual, queda de cabelo, hipoanorexia, indisposição, boca seca e irritabilidade, p<0,05). Em pacientes com hepatite C, a suplementação de cogumelo Agaricus brasiliensis (5g) por 24 semanas mostrou-se eficiente em reduzir a frequência...
Several studies indicate that the Agaricus brasiliensis is beneficial in various clinical conditions, such as hepatitis C. Several species of edible fungi have been explored as to its potential medical and many patients now have to seek a solution to their condition in complementary therapies. Objective: To evaluate the effects of supplementation of Agaricus brasiliensis on the nutritional status, the frequency of adverse effects of antiviral therapy and liver damage in patients with hepatitis C treated with pegylated interferon and ribavirin. We performed a prospective trial randomized controlled double-blind in the service of Viral Hepatitis Hospital of the Medical School of Botucatu, UNESP. Those in the study were subjected to a memorandum of supplementation with mushroom or placebo for 24 weeks, and were randomly distributed in the following groups: placebo-treated group (5g/dia n = 14) and mushroom-treated group (n 5g/dia- = 9). All tests were obtained before and after the treatments (placebo or mushroom). The nutritional status (anthropometric data, body composition, nutrition and biochemistry of food intake), was similar between the groups. There was improvement of liver damage in both groups, reducing transaminase (AST / ALT and AST / ALT, p <0.05), demonstrating the effectiveness of treatment antiviral use of the mushroom was shown to be beneficial in reducing the frequency and intensity of the adverse effects of drug therapy (myalgia, dysgeusia, headache, reduction in sexual desire, hair loss, hipoanorexia, malaise, dry mouth and irritability, p <0.05). In patients with hepatitis C, the supplementation of Agaricus brasiliensis (5) for 24 weeks proved to be effective in reducing the frequency and intensity of the adverse effects of drug therapy with pegylated interferon and ribavirin, and on the other hand, was inefficient for nutritional status and liver damage.
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Madelain, Vincent. "Modélisation de l’effet du favipiravir sur la dynamique viro-immunologique de la maladie à virus Ebola et implications pour son évaluation clinique." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC049.
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En dépit d’épidémies répétées, il n’existe pas à ce jour de thérapeutique ayant démontré son efficacité dans la maladie à virus Ebola. Sur la base d’expérimentations réalisées chez la souris et le macaque dans le cadre du consortium Reaction!, l’objectif de cette thèse visait à caractériser l’effet d’une molécule antivirale, le favipiravir, via l’implémentation de modèles mathématiques mécanistiques de l’infection et de la réponse immunitaire associée. L’approche utilisée pour construire ces modèles et en estimer les paramètres reposait sur les modèles non linéaires à effets mixtes. Un premier travail a permis d’explorer la relation concentration-effet sur la charge virale plasmatique chez la souris. Le second projet a conduit à caractériser la pharmacocinétique non linéaire dose et temps dépendante du favipiravir chez le macaque, en vue d’identifier les schémas posologiques pertinents pour la réalisation des études d’efficacité chez l’animal infecté. Au décours de leur réalisation, l’intégration des données virologiques et immunitaires générées au sein d’un modèle conjoint a permis de caractériser un effet modéré du favipiravir sur la réplication virale, mais suffisant pour limiter le développement d’une réaction inflammatoire délétère, et ainsi améliorer le taux de survie des animaux traités. Les simulations réalisées avec ce modèle ont pu souligner l’impact déterminant du délai d’initiation du traitement sur la survie. Ces résultats incitent à la poursuite de l’évaluation clinique du favipiravir, en favorisant des essais de prophylaxie ou post exposition. Enfin, un dernier travail a démontré l’absence de potentialisation du favipiravir par la ribavirine dans EbolaIn spite of recurrent outbreaks, no therapeutics with demonstrated clinical efficacy are available in Ebola virus disease. Based on experimentations performed by Reaction! Consortium in mice and macaques, this thesis aimed to characterize the effect of an antiviral drug, favipiravir, using mechanistic mathematical models of the infection and associated immune response. The approach to build models and estimate parameters relied on nonlinear mixed effect models. The first project of this thesis explored the concentration-effect relationship on the viremia in mice. Then, a second project allowed to characterize the pharmacokinetics of favipiravir in macaques, underlying dose and time non linearity, and to identify relevant dosing regimen for efficacy experiments in infected animals. Once these experiments completed, the integration of the virological and immunological data into a mechanistic joint model shed light on the effect of favipiravir. The moderate inhibition of the viral replication resulting from the favipiravir plasma concentrations was enough to limit the development of a deleterious inflammatory response, and thus improve the survival rate of treated macaques. Simulations performed with this model underlined the crucial impact of the treatment initiation delay on survival. These results encourage the pursuit of the clinical evaluation of favipiravir in prophylaxis or post exposure trials. Finally, a last project demonstrated the lack of benefit of ribavirin addition to favipiravir in Ebola virus disease
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Silhol, Michelle. "La microinjection dans les cellules somatiques : effet d'agents antiviraux." Montpellier 2, 1987. http://www.theses.fr/1987MON20232.
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Silhol, Michelle. "La Microinjection dans les cellules somatiques effet d'agents antiviraux /." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37609920n.
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Wagner, Gerhardt Stefan. "Generation of antiviral, effector CD4+ T cells : a novel vaccine strategy against HIV /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2003. http://uclibs.org/PID/11984.
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Welsch, Hendrik [Verfasser], and Marco [Akademischer Betreuer] Binder. "Investigating the Effects of Chronic Stimulation of Innate Antiviral Immune Responses / Hendrik Welsch ; Betreuer: Marco Binder." Heidelberg : Universitätsbibliothek Heidelberg, 2021. http://nbn-resolving.de/urn:nbn:de:bsz:16-heidok-305387.
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Knorr, Corinna W. "Characterization of Cytokine Induction and Effects of Antiviral Treatment in Four Murine Models of Poxvirus Infection." DigitalCommons@USU, 2005. https://digitalcommons.usu.edu/etd/4671.
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Cytokine profiles during cowpox virus (CPV) strain Brighton and vaccinia virus (VV) strain Western Reserve infections were characterized in intranasal (i.n.) and intraperitoneal (i .p.) models in BALB/c mice. The time-course of induction and effects of cidofovir treatment on interferon (IFN)-γ, IFN-γ inducible protein (IP)-10, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 were determined. The four models have distinct patterns of cytokine induction. CPV i.p. and VV i.n. infections showed increased induction throughout the time studied. CPV i.n. infection resulted in delayed induction of IFN-γ and IP-10. Cytokine levels were fairly constant during VV i.p. infections. Cidofovir treatment (100 mg/kg/day i.p. for 2 days) significantly reduced certain cytokine levels in the four models. Treatment did not affect IP-10 in the CPV i.n. model; IFN-γ and IP-10 in the CPV i.p. model; or IL-6, IP- 10, and MCP-1 in the VV i.p. model. Characterization of cytokine responses has implications for understanding the immune responses and pathogeneses of viral infections in these models.
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Saulnier, Aure. "Effet antiviral de siRNA dans des modèles d'infections lytiques et persistantes par des virus à RNA positif." Paris 6, 2006. http://www.theses.fr/2006PA066083.
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McFarlane, Amanda Jayne. "Effects of the strictly enteric helminth, Heligmosomoides polygyrus, on respiratory syncytial virus (RSV) infection." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17625.
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RSV is the most common cause of infant bronchiolitis, leading to morbidity and mortality in both infants and the elderly. The relationship between RSV and asthma development further highlights the need to fully understand the immune responses involved in order to develop effective vaccines and therapeutics to aid prevention and treatment of RSV infection respectively. Helminths have long been studied both as a major pathogen of humans, infecting approximately 3 billion people worldwide, and also their ability to modulate the host immune response to allow survival and chronic infection to ensue. Specifically, helminth infections are thought to modulate the host immune response through regulatory mechanisms which are not fully understood. This not only confers protection and survival of the parasites themselves, but also modulates the immune response to unrelated antigens and pathogens. In this thesis, the potential role of a strictly enteric helminth infection, with Heligmosomoides polygyrus, in the modulation of respiratory syncytial virus (RSV) infection was investigated and the associated immune mechanisms were investigated. Firstly, the effects of prior H. polygyrus infection on RSV infection and immune responses in the lung were analysed. H. polygyrus significantly reduced the number of natural killer cells, CD8+ T cells, B cells and conventional dendritic cells in the lung following RSV infection. Co-infection also reduced the production of pro-inflammatory cytokines IL-6 and TNF-α in the lungs. All of these reductions were associated with significantly lower viral titres on day 4 of RSV infection. Interestingly, this attenuation of immune responses and viral titres, correlated with reduced severity of clinical disease, as assessed by weight loss and lung function. H. polygyrus excretory secretory product (HES) was not found to be the immune-modulatory factor in this system, as HES failed to suppress viral titres and reduce immune cell responses to RSV infection. However, irradiated larvae with stunted maturation to adult worms, revealed that larval stages were sufficient to suppress viral titres. Next, the role of type 2 signalling for H. polygyrus effects on RSV infection were examined, using IL-4Rα-/- mice. H. polygyrus infection maintained the ability to attenuate RSV infection and subsequent immune responses in IL-4Rα-/- mice. Furthermore, the presence of the adaptive immune response was not required for H. polygyrus-induced attenuation of RSV infection, as demonstrated in recombinase-activating gene (RAG-/-) deficient mice. H. polygyrus induces innate type 2 immune responses indicating the release of the innate alarmin, IL-33, in the lung and consequently an accumulation of group 2 innate lymphoid cells (ILC2). Their contribution to H. polygyrus effects remain to be fully elucidated. Finally, the role of antiviral responses was explored in H. polygyrus and RSV co-infection. H. polygyrus infection alone induced expression of antiviral genes, IFN-β, OAS1A, Viperin and the antimicrobial peptide CRAMP, in both the duodenum and the lung. Expression of these genes was still higher in the lung 1 hour after RSV in H. polygyrus co-infected mice compared to controls without co-infection. The importance of type I IFN signalling pathway was demonstrated using mice deficient in the type I IFN receptor in H. polygyrus co-infection, which failed to suppress RSV titres and subsequent lung immune cell infiltration. These data highlight the ability of the strictly enteric helminth H. polygyrus to attenuate RSV infection and subsequent immune responses in the lung through the potentiation of type I IFN signalling and consequent upregulation of antiviral immune responses in the lung.
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Kalogirou, Maria. "Antiviral and quality effects of chemical elictors and Cucumber Mosaic Virus (CMV) infection on tomato plants and fruits." Thesis, Cranfield University, 2012. http://dspace.lib.cranfield.ac.uk/handle/1826/7278.
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Cucumber mosaic virus (CMV) has emerged as one of the most serious threats to tomato cultivation in Greece. In the present study the effects of Benzothiadiazoles (BTH) and pyraclostrobin against mechanically or aphid-transmitted CMV in tomato plants, of hybrid F1 Clodin, were investigated in greenhouse experiments. BTH was confirmed as capable of inducing systemic acquired resistance (SAR) in tomato seedlings against CMV, while pyraclostrobin was not. Responses to BTH application and/or CMV inoculation on Spanish tomato hybrid Delos (BTH, BTH+CMV, CMV treatments) were monitored during winter and spring season in Greece. In both seasons the SAR derived from BTH application suppressed CMV. BTH treatment presented increased plant growth, fruit size and marketable tomato yield compared to CMV and BTH+CMV treatments, whereas decreased compared to healthy control. CMV treatment caused the most severe stunting of tomato plants among the examined treatments and resulted in yield loss of marketable fruits, although the total fruit number was higher versus to other treatments. Cont/d.
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Béchard-Dubé, Steffi-Anne. "Effets de l'environnement lumineux et de l'âge foliaire sur la croissance, la capacité photosynthétique et la production protéique chez Nicotiana benthamiana." Master's thesis, Université Laval, 2015. http://hdl.handle.net/20.500.11794/26972.
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Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2015-2016Cette étude visait à caractériser la croissance, la capacité photosynthétique, la concentration en azote et protéines totales solubles, la production de protéines recombinantes (HA) ainsi que la quantité de lumière interceptée à différents stades de développement de plants de Nicotiana benthamiana afin d’optimiser la production de vaccins. L’évolution des réponses physiologiques étudiées fut similaire chez toutes les feuilles primaires, suggérant que le processus de sénescence s’initie et progresse de façon semblable indépendamment de leur ordre d’initiation. Toutefois, la superposition des patrons temporels de sénescence et de croissance foliaire a mené à un rendement HA maximal se situant invariablement dans la partie médiane du plant lorsqu’exprimé sur une base foliaire. À l’échelle du plant entier, nos résultats suggèrent qu’il est possible d’augmenter la production de vaccins en récoltant les plants à un stade de développement plus tardif, ou en augmentant la densité de culture et en récoltant ces plants plus tôt.
Nicotiana benthamiana is a wild relative of tobacco increasingly used as a plant protein expression platform to produce recombinant vaccine antigens against the influenza virus. Investigation on the physiological determinants of this production is essential to optimize and regulate vaccines production following a new flu outbreak. We examined the photosynthetic photon flux density, growth, light-saturated photosynthesis, total soluble protein, nitrogen content and recombinant protein production at different phenological stages. The similar evolution of the studied physiological responses suggested that the senescence process is initiated and progresses in a similar way in all primary leaves, regardless of the order of initiation. In contrast, the superposition of the time pattern of senescence with that of leaf growth shows that maximal HA yield expressed on a leaf basis is invariably located in the middle part of the plant. At the whole plant scale, our results suggest that it is possible to increase the production of antigens by harvesting plants at a later developmental stage, or by increasing plant density and harvesting these plants earlier.
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Cornacini, Milena Costa Menezes. "Efeito do uso do cogumelo Agaricus brasiliensis no estado nutricional, na frequência e intensidade dos efeitos adversos da terapia medicamentosa e na resposta bioquímica hepática em indivíduos com hepatite crônica pelo vírus C : estudo prospectivo, randomizado, duplo cego, placebo controlado /." Botucatu : [s.n.], 2009. http://hdl.handle.net/11449/102636.
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Resumo: Diversos estudos, indicam que o cogumelo Agaricus brasiliensis é benéfico em várias condições clínicas, como na hepatite C. Várias espécies de cogumelos comestíveis têm sido exploradas quanto ao seu potencial medicinal e muitos pacientes passam a buscar a solução para suas patologias nas terapias complementares. Avaliar os efeitos da suplementação do Agaricus brasiliensis sobre o estado nutricional, a frequência e a intensidade dos efeitos adversos da terapia antiviral e a resposta bioquímica hepática em indivíduos com hepatite C em tratamento com Interferon peguilado e Ribavirina. Foi realizado um ensaio clínico prospectivo controlado casualizado duplo cego no Serviço de Hepatites Virais do Hospital das Clínicas da Faculdade de Medicina de Botucatu-UNESP. Os indivíduos do estudo foram submetidos a um protocolo de suplementação com cogumelo ou placebo por 24 semanas, e foram distribuídos aleatoriamente nos seguintes grupos: Grupo tratado com placebo (5g/dia n=14) e Grupo tratado com cogumelo (5g/dian= 9).Todas as análises foram obtidas antes e após os tratamentos (placebo ou cogumelo). O estado nutricional (dados antropométricos, de composição corporal, da bioquímica nutricional e do consumo alimentar), foi semelhante entre os grupos. Houve melhora da lesão hepática em ambos os grupos, com redução de transaminases (TGO/AST e TGP/ALT, p<0,05), mostrando a eficácia do tratamento antiviral.O uso do cogumelo mostrou-se benéfico na redução da frequência e intensidade dos efeitos adversos da terapia medicamentosa (mialgia, disgeusia, cefaléia, redução do desejo sexual, queda de cabelo, hipoanorexia, indisposição, boca seca e irritabilidade, p<0,05). Em pacientes com hepatite C, a suplementação de cogumelo Agaricus brasiliensis (5g) por 24 semanas mostrou-se eficiente em reduzir a frequência... (Resumo completo, clicar acesso eletrônico abaixo)Abstract: Several studies indicate that the Agaricus brasiliensis is beneficial in various clinical conditions, such as hepatitis C. Several species of edible fungi have been explored as to its potential medical and many patients now have to seek a solution to their condition in complementary therapies. Objective: To evaluate the effects of supplementation of Agaricus brasiliensis on the nutritional status, the frequency of adverse effects of antiviral therapy and liver damage in patients with hepatitis C treated with pegylated interferon and ribavirin. We performed a prospective trial randomized controlled double-blind in the service of Viral Hepatitis Hospital of the Medical School of Botucatu, UNESP. Those in the study were subjected to a memorandum of supplementation with mushroom or placebo for 24 weeks, and were randomly distributed in the following groups: placebo-treated group (5g/dia n = 14) and mushroom-treated group (n 5g/dia- = 9). All tests were obtained before and after the treatments (placebo or mushroom). The nutritional status (anthropometric data, body composition, nutrition and biochemistry of food intake), was similar between the groups. There was improvement of liver damage in both groups, reducing transaminase (AST / ALT and AST / ALT, p <0.05), demonstrating the effectiveness of treatment antiviral use of the mushroom was shown to be beneficial in reducing the frequency and intensity of the adverse effects of drug therapy (myalgia, dysgeusia, headache, reduction in sexual desire, hair loss, hipoanorexia, malaise, dry mouth and irritability, p <0.05). In patients with hepatitis C, the supplementation of Agaricus brasiliensis (5) for 24 weeks proved to be effective in reducing the frequency and intensity of the adverse effects of drug therapy with pegylated interferon and ribavirin, and on the other hand, was inefficient for nutritional status and liver damage.
Orientador: Carlos Antonio Caramori
Coorientador: Maria Antonieta de Barros Leite Carvalhaes
Banca: Giovanni Faria Silva
Banca: Ana Lúcia T. Spinardi Barbisan
Banca: Lucienne de Souza Venâncio Lotufo Brant
Banca: Anderson Merliere Navarro
Doutor
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Defilippi, Paola M. "Regulation of the expression of genes induced by IFN, IL-1 and TNF and their implication in antiviral effects." Doctoral thesis, Universite Libre de Bruxelles, 1986. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/213557.
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COUFFIN, ANNE CLAUDE. "Association du poly(l-lysine citramide) avec une antiprotease du vih et evaluation de l'activite antivirale sur cellules infectees." Montpellier 2, 2000. http://www.theses.fr/2000MON20036.
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Cette these visait a vectoriser un inhibiteur de la protease du vih via une association avec le poly(l-lysine citramide), vecteur macromoleculaire hydrosoluble, biocompatible et bioresorbable afin de favoriser la penetration intracellulaire du principe actif a faible biodisponibilite. Le memoire debute par un rappel bibliographique des connaissances sur la protease du vih et sur les systemes macromoleculaires vecteurs potentiels d'inhibiteurs de la protease. Le chapitre ii est consacre a une nouvelle voie de synthese du poly(l-lysine citramide) en phase homogene, et a la caracterisation du vecteur obtenu. Par comparaison avec la polycondensation interfaciale, il est montre que les polymeres prepares par les deux voies sont de meme nature chimique mais different par la proportion des unites de type imide et oxolactone. Le chapitre iii rapporte la synthese et la caracterisation de conjugues polymere plca/inhibiteur (psi) ou non inhibiteur (pni) de la protease du vih via l'agent de couplage bop. Une etude physico-chimique de ces conjugues renseigne sur leur comportement en milieu aqueux. Afin de distinguer l'influence de la nature macromoleculaire des conjugues au cours des tests cellulaires, des composes modeles des unites constitutives de la prodrogue macromoleculaire sont synthetises et etudies comparativement (cipsi et lypsi). Le chapitre iv traite de l'evaluation in vitro de l'activite antivirale des conjugues et de leur comportement au contact de cellules infectees par le vih. L'interaction vecteurs synthetiques/cellules infectees est etudiee. Afin d'envisager une eventuelle exploitation therapeutique, l'absence de toxicite d'un conjugue in vivo est verifiee. Il est montre que l'activite antivirale est en fait liee a la nature macromoleculaire des conjugues et non a un comportement de prodrogues.
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Rocquigny, Hugues de. "Caractérisation moléculaire des domaines fonctionnels des nucléoprotéines NCp7 et NCp10 des rétrovirus HIV-1 et MoMuLV : synthèse chimique, études biochimique et structurale." Paris 5, 1993. http://www.theses.fr/1993PA05P630.
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Aljabr, Waleed A. "Using label free proteomics and RNA sequencing to investigate the human respiratory syncytial virus and the effects of the antiviral ribavirin." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3004499/.
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Human respiratory syncytial virus (HRSV) is a known cause of severe lower respiratory tract infection (LRTI) in infants and young children worldwide. HRSV can cause illness in all ages especially those people at high risk including the immunocompromised and the elderly. Globally, HRSV infection leads to a significant healthcare and economic burden due to the lack of an approved vaccine and costly antiviral therapies that are potentially ineffective in some cases. Ribavirin is the only therapeutic licensed for the treatment of severe HRSV infection. It is a synthetic nucleoside with broad spectrum of antiviral activity encompassing both DNA and RNA viruses. The mechanism of action of ribavirin is unclear. It is thought to inhibit the replication of HRSV and lead to a reduction in viral load. How it does this is unknown and the subject of this thesis. This study focused on investigating the effect of the anti-viral ribavirin on cells in general and then infected with HRSV using both label free quantitative proteomics and transcriptomics. This allowed the investigation of the mutation frequency in HRSV and cellular protein abundance, which encompass several mechanisms by which ribavirin is postulated to work. This study was demonstrated that treatment of cells with ribavirin resulted in the increased transcription of selected cellular mRNAs including those involved in mediating anti-viral signalling. Additionally, ribavirin treatment caused a decrease in viral mRNA and proteins. In the absence of ribavirin, HRSV specific transcripts accounted for up to one third of total RNA reads from the infected cell RNA population. Ribavirin treatment resulted in a greater than 90% reduction in reads mapping to viral mRNA, while at the same time no such drastic reduction was detected for the abundance of cellular transcripts. The presented data revealed that ribavirin significantly increased the frequency of HRSV-specific RNA mutations in the viral genome, suggesting direct influence on the fidelity of the HRSV polymerase. The presented data shows transition and transversion substitutions occur during HRSV replication, and that these changes occurred in 'hot spots' along the HRSV genome. Examination of nucleotide substitution rates in the viral genome indicated an increase in the frequency of transition but not transversion mutations in the presence of ribavirin. In addition, the data indicated that in the continuous cell types used, and at the time points analyzed, the abundance of some HRSV mRNAs did not reflect the order in which the mRNAs were transcribed. Overall, the work describes a mechanism of action for ribavirin in the context of viral infection, that has not previously been elucidated for HRSV.
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Klages, Michael [Verfasser]. "Der antivirale Effekt des T-Zell-Zytokins Interleukin-26 auf die Infektion mit dem humanen Cytomegalovirus / Michael Klages." Kiel : Universitätsbibliothek Kiel, 2016. http://d-nb.info/1111558663/34.
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Trout, Hervé. "Pharmacocinétique de population et absorption digestive de médicaments du SIDA : application aux antiviraux et médicaments associés." Paris 5, 1999. http://www.theses.fr/1999PA05P605.
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Belmonte, Antonietta. "The effects of antiviral therapy on the levels of neutralizing antibodies and antibodies mediating antibody-dependent cellular cytotoxicity in HI-1 seropositive patients /." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56983.
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This study consists of evaluating the effects of zidovudine or ribavirin treatment on the humoral response to human immunodeficiency syndrome (HIV-1) in a cohort of 36 HIV-1 seropositive patients. Viral neutralization antibodies were demonstrated against HTLV$ sb{ rm IIIb}$ virus while titers of circulating antibody-dependent cellular cytotoxicity (ADCC) antibodies were measured against the HIV-1 envelope protein, gp120, using the vaccinia virus expression system which has been successfully used to express foreign viral proteins in target cells. Virologic (viral isolation) and immunologic (CD4$ sp+$ cells) parameters were also monitored pre and post antiviral therapy.The results indicate that patients receiving zidovudine for 36 weeks, have a diminished anti-HIV-1-ADCC directing antibody response, while the levels of these antibodies in patients receiving ribavirin or placebo remain constant. The titers of neutralizing antibodies and CD4 counts remain stable regardless of the treatment except for patients receiving ribavirin, where a decline in CD4 cells is observed. The decrease in the HIV-1 specific ADCC during zidovudine treatment parallels with the decrease in the amount of viral burden. This suggests that the two effects are somehow correlated. The impact of a washout period was also assessed. An increase in viral burden during cessation of AZT was reported which may reflect the inability of the treated host to mount a rapid immune response. As a consequence, this may lead to the deterioration of the immune status and the progression of the disease. The implications of these findings will be discussed in this study.
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Meunier, Thomas. "Étude des mécanismes d’action de nouveaux inhibiteurs de coronavirus humains." Thesis, Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS057.
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Les coronavirus sont des virus ARN enveloppés qui infectent les mammifères et les oiseaux. Chez l’homme, quatre coronavirus causent des maladies bénignes comme des rhumes et rhinites, HCoV-OC43, HCoV-229E, HCoV-NL63 et HCoV-HKU1. Au cours des deux dernières décennies, trois nouveaux coronavirus hautement pathogènes ont été identifiés, le SARS-CoV (« Severe Acute Respiratory Syndrome ») en 2003, le MERS-CoV (« Midle East Respiratory Syndrome ») en 2012 et récemment le SARS-CoV-2 en décembre 2019. La pandémie mondiale du COVID-19 a mis en évidence le manque d’antiviraux ciblant les coronavirus. Bien que de nombreux vaccins efficaces soient développés pour contrer la pandémie de COVID-19 due au SARS-CoV-2, il n’y a toujours aucun antiviral spécifique commercialisé contre ce virus et les traitements actuels consistent à traiter uniquement les symptômes.L’équipe du Dr Karin SERON du laboratoire de Virologie Moléculaire et Cellulaire du Centre d’Infection et d’Immunité de Lille s’est spécialisée dans l’identification d’antiviraux d’origine naturelle. En effet les plantes sont une source importante de molécules thérapeutiques et de nombreuses plantes sont encore utilisées aujourd’hui en médecine traditionnelle. L’objectif de ma thèse a été d’utiliser les connaissances et techniques développées par le laboratoire pour identifier des antiviraux naturels contre les coronavirus humains hautement pathogènes et de comprendre leurs mécanismes d’action. Mon premier projet a été réalisé en collaboration avec le groupe de Dr Simon Bordage du laboratoire de Pharmacognosie de la Faculté de Pharmacie de Lille dirigé par le Pr Sevser Sahpaz. Suite au criblage d’extraits de plantes, utilisées en médecine traditionnelle ivoirienne, contre le coronavirus HCoV-229E, nous avons sélectionné l’extrait de Mallotus oppositifollius qui était le plus actif. Après un fractionnement bioguidé, le principe actif a été isolé et identifié. Il s’agit du phéophorbide a (Pba). Le Pba inhibe HCoV-229E mais aussi les coronavirus hautement pathogènes MERS-CoV et SARS-CoV-2 (IC50 = 0,18 μM) ainsi que d’autres virus enveloppés par un mécanisme de photo-inactivation dynamique. Nous avons montré que le Pba cible la membrane virale et inhibe l’étape de fusion. Le Pba est le premier antiviral naturel possédant une activité virucide photo-dépendante décrite contre le SARS-CoV-2. Cette molécule pourrait potentiellement être utilisée en thérapie clinique ou comme désinfectant de surface. Mon deuxième projet porte sur une anthocyanidine, la delphinidine, déjà décrite par notre laboratoire comme antiviral contre le virus de l’hépatite C. Nous avons montré que la delphinidine inhibe de façon dose-dépendante l’entrée des coronavirus HCoV-229E, MERS-CoV et SARS-CoV-2 dans les cellules (IC50 = 16-20 μM). Nos résultats montrent que la delphinidine cible les sites de glycosylation de la protéine de surface S. Grâce à une collaboration avec le laboratoire de Chimie Bio-organique et Médicinale de Strasbourg, dirigé le Dr Mourad Elhabiri, nous avons criblé des dérivés de la delphinidine afin d’identifier des molécules plus actives. Nous avons ainsi identifié un composé actif contre le HCoV-229E à une concentration très faible (IC50 = 0,06 μM) mais qui semble avoir un mécanisme d’action différent de la delphinidine. En effet, il est actif à l’étape de réplication.En conclusion, au cours de ma thèse j’ai pu identifier de nouveaux antiviraux naturels contre les coronavirus humains et notamment le SARS-CoV-2 ayant des mécanismes d’action inédits. Ces travaux pourront servir de base à l’obtention de molécules pouvant être utilisées, dans l’avenir, pour le traitement des maladies à coronavirusCoronaviruses are enveloped RNA viruses infecting mammals and birds. Four coronaviruses causing mild diseases, like common cold, have been described in human, HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1. During the last two decades, three new, highly pathogenic coronaviruses have been identified the SARS-CoV (Severe Acute Respiratory Syndrom) in 2003, the MERS-CoV (Middle East Respiratory Syndrome) in 2012 and recently the SARS-CoV-2 in December 2019. The COVID-19 global outbreak caused by SARS-CoV-2, highlighted the lack of specific antiviral available against this family of virus. The team of Dr Karin SERON from the Cellular and Molecular Virology laboratory of the Center for Infection and Immunity of Lille, is specialized in the identification of antiviral compounds from natural origin. Indeed, plants are a source of natural therapeutic compounds and many plants are still being used in traditional medicine. The aim of my thesis was to identify natural antiviral agents against highly pathogenic human coronaviruses with the help of the knowledge and tools developed by the laboratory. My first project was carried out in collaboration with the group of Dr Simon Bordage from the Pharmacognosy laboratory of the Faculty of Pharmacy of Lille directed by Pr Sevser Sahpaz. Plant extracts from Ivorian plants used it traditional medicine were tested against the coronavirus HCoV-229E and we selected the most active, the Mallotus oppositifollius extract. After bio-guided fractionation, the active compound was isolated and characterized, the pheophorbide a (Pba). Pba is able to inhibit the infection of HCoV-229E and highly pathogenic coronaviruses MERS-CoV and SARS-CoV-2 (IC50 = 0.18 μM) as well as other enveloped viruses using a photo-dynamic inactivation mechanism. Pba targets the viral envelop and inhibits the fusion step. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity. This molecule could potentially be used in therapy or as disinfectant. My second project was about an anthocyanidin, the delphinidin, identified in the laboratory for its antiviral activity against hepatitis C virus. We showed that delphinidin is an entry inhibitor of coronaviruses in a dose-dependent manner for HCoV-229E, MERS-CoV and SARS-CoV-2 (IC50 = 16-20 μM). Our results show that delphinidin targets the glycosylation sites on the surface protein S. Thanks to a collaboration with the laboratory of Medicinal and Bioorganic Chemistry of Strasbourg, led by Dr Mourad Elhabiri, delphinidin synthetic derivates were screened in order to identify compounds with higher antiviral capacities. We thereby identify an active compound against HCoV-229E with a lower IC50 than delphinidin (IC50 = 0.06 μM). Surprisingly, its mechanism of action seems to be different than delphinidin with an activity at the replication step.In conclusion, during my thesis I was able to identify new natural antivirals against human coronaviruses, and in particular SARS-CoV-2, with novel mechanisms of action. This work may serve as a basis for obtaining molecules that can be used in the future for the treatment of coronavirus diseases
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Gamlen, Toby Philip Edward. "Non-structural proteins derived from non-cytopathic or cytopathic biotypes of bovine viral diarrhoea virus have distinct effects on cell survival and antiviral signalling pathways." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435778.
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