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1

Decombe, Alice, Priscila El-Kazzi, Sébastien Nisole, and Étienne Decroly. "Effets de la 2′-O-méthylation de l’ARN génomique du VIH-1 sur la réplication virale." médecine/sciences 40, no. 5 (May 2024): 421–27. http://dx.doi.org/10.1051/medsci/2024046.

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Les ARN du virus de l’immunodéficience humaine sont décorés par des marques épitranscriptomiques, dont des 2′-O-méthylations internes. Ces marques ajoutées par une enzyme cellulaire, FTSJ3, sont des marqueurs du « soi ». Elles ont des effets proviraux en protégeant l’ARN viral de la détection par le senseur de l’immunité innée MDA5, et en limitant sa dégradation par l’exonucléase cellulaire ISG20, induite par l’interféron. Ces méthylations ont également un effet antiviral, dans la mesure où elles perturbent la rétrotranscription du génome ARN du virus, in vitro et dans des cellules quiescentes. Un équilibre subtil existe donc entre les effets proviraux et antiviraux des 2′-O-méthylations, assurant ainsi une réplication optimale du virus. Ces découvertes ouvrent des perspectives d’optimisation des ARN thérapeutiques à effet antiviral, par la méthylation sélective de certains nucléotides.
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2

Jegado, Brice, Chloé Journo, and Renaud Mahieux. "Un double effet antiviral des IFITM sur les virus enveloppés." médecine/sciences 34, no. 3 (March 2018): 214–18. http://dx.doi.org/10.1051/medsci/20183403008.

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3

D’Alteroche, Louis, Philippe Assor, Laurent Lefrou, Delphine Senecal, Catherine Gaudy, and Yannick Bacq. "Neutropénie et thrombopénie auto-immunes sévères associées à une hépatite chronique C : effet du traitement antiviral." Gastroentérologie Clinique et Biologique 29, no. 3 (March 2005): 297–99. http://dx.doi.org/10.1016/s0399-8320(05)80766-3.

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4

Ongaro, Marie, and Francesco Negro. "Hépatite B et C: une mise à jour sur lʼhépatite virale chronique." Schweizer Gastroenterologie 3, no. 1 (March 2022): 19–27. http://dx.doi.org/10.1007/s43472-022-00062-6.

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RésuméL’hépatite virale est une problématique de santé publique majeure contre laquelle l’organisation mondiale de la santé (OMS) a proposé de nombreuses stratégies pour son élimination. Malgré de nombreuses avancées thérapeutiques, il reste des freins pour atteindre les objectifs ambitieux proposés par l’OMS. Concernant le virus de l’hépatite B (VHB), un effort doit être fourni pour promouvoir la vaccination universelle et réduire le risque de transmission materno-fœtale. La recherche d’un traitement curatif est également à considérer et nous passerons brièvement en revue les avancées dans ce domaine.L’élimination du virus de l’hépatite C (VHC) rencontre des difficultés différentes. En effet, malgré la disponibilité d’un traitement antiviral efficace dirigé contre le VHC, les données récentes montrent que seulement 5 % de la population mondiale diagnostiquée aurait bénéficié d’un traitement. Les stratégies actuelles doivent axer leurs efforts sur l’accès au circuit de soin pour les patients virémiques. Une autre difficulté réside dans le suivi des patients guéris avec des recommandations de suivi encore débattues.Cette revue passera rapidement en revue les avancées récentes concernant les virus de l’hépatite B et C.
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5

Glass, Kathryn, and Niels G. Becker. "Estimating antiviral effectiveness against pandemic influenza using household data." Journal of The Royal Society Interface 6, no. 37 (December 5, 2008): 695–703. http://dx.doi.org/10.1098/rsif.2008.0404.

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Current estimates of antiviral effectiveness for influenza are based on the existing strains of the virus. Should a pandemic strain emerge, strain-specific estimates will be required as early as possible to ensure that antiviral stockpiles are used optimally and to compare the benefits of using antivirals as prophylaxis or to treat cases. We present a method to measure antiviral effectiveness using early pandemic data on household outbreak sizes, including households that are provided with antivirals for prophylaxis and those provided with antivirals for treatment only. We can assess whether antiviral drugs have a significant impact on susceptibility or on infectivity with the data from approximately 200 to 500 households with a primary case. Fewer households will suffice if the data can be collected before case numbers become high, and estimates are more precise if the study includes data from prophylaxed households and households where no antivirals are provided. Rates of asymptomatic infection and the level of transmissibility of the virus do not affect the accuracy of these estimates greatly, but the pattern of infectivity in the individual strongly influences the estimate of the effect of antivirals on infectivity. An accurate characterization of the infectiousness profile—informed by strain-specific data—is essential for measuring antiviral effectiveness.
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6

Ningrum, Andi Utari Prasetya, Retnosari Andrajati, Nadia Farhanah Syafhan, and Aditya Wirawan. "Effectiveness of COVID-19 Antivirus Therapy and Its Relationship with Vaccination: A Retrospective Analysis." Jurnal Respirologi Indonesia 43, no. 3 (July 31, 2023): 195–203. http://dx.doi.org/10.36497/jri.v43i3.434.

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Background: COVID-19 is known to have infected more than a million people. COVID-19 can be treated with antivirals. Besides antiviral drugs, vaccination becomes one of the strategies to suppress the spread of COVID-19. This study aimed to analyze the effectiveness of antivirus and the relationship between vaccination and the effectiveness of the two antiviral therapies in COVID-19 patients based on improvements in the patient's clinical condition, length of stay, and mortality.Methods: This study used a retrospective cohort design conducted at the Universitas Indonesia Hospital, Depok, Indonesia. Data were taken from medical records and hospital databases from January 2021 to August 2022. The antivirals in this study were remdesivir and favipiravir. The samples were divided into two groups, namely the vaccinated and unvaccinated groups.Results: The factor affecting the effectiveness of remdesivir and favipiravir therapy was the severity of COVID-19. It was shown that vaccination had a significant effect on improving clinical conditions, reducing length of stay, and reducing mortality in patients treated with remdesivir who had been vaccinated compared to those who had not been vaccinated. In patients who received favipiravir therapy and were vaccinated, it also showed an effect on improving clinical conditions, length of stay, and mortality compared to patients who were not vaccinated, although the results were not statistically significant.Conclusion: Vaccination had a positive effect on the effectiveness of remdesivir and favipiravir in COVID-19 patients, which could improve the patient's clinical condition in a better direction, as well as reduce length of hospitalization and mortality.
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7

Alexander, Paul, and Hana M. Dobrovolny. "Treatment of Respiratory Viral Coinfections." Epidemiologia 3, no. 1 (February 23, 2022): 81–96. http://dx.doi.org/10.3390/epidemiologia3010008.

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With the advent of rapid multiplex PCR, physicians have been able to test for multiple viral pathogens when a patient presents with influenza-like illness. This has led to the discovery that many respiratory infections are caused by more than one virus. Antiviral treatment of viral coinfections can be complex because treatment of one virus will affect the time course of the other virus. Since effective antivirals are only available for some respiratory viruses, careful consideration needs to be given on the effect treating one virus will have on the dynamics of the other virus, which might not have available antiviral treatment. In this study, we use mathematical models of viral coinfections to assess the effect of antiviral treatment on coinfections. We examine the effect of the mechanism of action, relative growth rates of the viruses, and the assumptions underlying the interaction of the viruses. We find that high antiviral efficacy is needed to suppress both infections. If high doses of both antivirals are not achieved, then we run the risk of lengthening the duration of coinfection or even of allowing a suppressed virus to replicate to higher viral titers.
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8

Gao Bin and Yang Gui-zhen. "Immunoregulatory effect and antitumor, antiviral, antivirus activity of polysaccharide." International Journal of Immunopharmacology 13, no. 6 (January 1991): 731. http://dx.doi.org/10.1016/0192-0561(91)90235-y.

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9

Chandra, Naresh, Lars Frängsmyr, and Niklas Arnberg. "Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus." Viruses 11, no. 3 (March 12, 2019): 242. http://dx.doi.org/10.3390/v11030242.

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Epidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available for the treatment of EKC. Recently, we have reported that sulfated glycosaminoglycans (GAGs) bind to HAdV-D37 via the fiber knob (FK) domain of the viral fiber protein and function as decoy receptors. Based on this finding, we speculated that GAG-mimetics may act as artificial decoy receptors and inhibit HAdV-D37 infection. Repurposing of approved drugs to identify new antivirals has drawn great attention in recent years. Here, we report the antiviral effect of suramin, a WHO-approved drug and a widely known GAG-mimetic, against HAdV-D37. Commercially available suramin analogs also show antiviral effects against HAdV-D37. We demonstrate that suramin exerts its antiviral activity by inhibiting the attachment of HAdV-D37 to cells. We also reveal that the antiviral effect of suramin is HAdV species-specific. Collectively, in this proof of concept study, we demonstrate for the first time that virus binding to a decoy receptor constitutes a novel and an unexplored target for antiviral drug development.
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Langendries, Lana, Rana Abdelnabi, Johan Neyts, and Leen Delang. "Repurposing Drugs for Mayaro Virus: Identification of EIDD-1931, Favipiravir and Suramin as Mayaro Virus Inhibitors." Microorganisms 9, no. 4 (March 31, 2021): 734. http://dx.doi.org/10.3390/microorganisms9040734.

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Despite the emerging threat of the Mayaro virus (MAYV) in Central and South-America, there are no licensed antivirals or vaccines available for this neglected mosquito-borne virus. Here, we optimized a robust antiviral assay based on the inhibition of the cytopathogenic effect that could be used for high-throughput screening to identify MAYV inhibitors. We first evaluated different cell lines and virus inputs to determine the best conditions for a reliable and reproducible antiviral assay. Next, we used this assay to evaluate a panel of antiviral compounds with known activity against other arboviruses. Only three drugs were identified as inhibitors of MAYV: β-D-N4-hydroxycytidine (EIDD-1931), favipiravir and suramin. The in vitro anti-MAYV activity of these antiviral compounds was further confirmed in a virus yield assay. These antivirals can therefore serve as reference compounds for future anti-MAYV compound testing. In addition, it is of interest to further explore the activity of EIDD-1931 and its orally bioavailable pro-drug molnupiravir in animal infection models to determine whether it offers promise for the treatment of MAYV infection.
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11

Chung, Dong-Hoon, Jennifer E. Golden, Robert S. Adcock, Chad E. Schroeder, Yong-Kyu Chu, Julie B. Sotsky, Daniel E. Cramer, et al. "Discovery of a Broad-Spectrum Antiviral Compound That Inhibits Pyrimidine Biosynthesis and Establishes a Type 1 Interferon-Independent Antiviral State." Antimicrobial Agents and Chemotherapy 60, no. 8 (May 16, 2016): 4552–62. http://dx.doi.org/10.1128/aac.00282-16.

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ABSTRACTViral emergence and reemergence underscore the importance of developing efficacious, broad-spectrum antivirals. Here, we report the discovery of tetrahydrobenzothiazole-based compound 1, a novel, broad-spectrum antiviral lead that was optimized from a hit compound derived from a cytopathic effect (CPE)-based antiviral screen using Venezuelan equine encephalitis virus. Compound 1 showed antiviral activity against a broad range of RNA viruses, including alphaviruses, flaviviruses, influenza virus, and ebolavirus. Mechanism-of-action studies with metabolomics and molecular approaches revealed that the compound inhibits host pyrimidine synthesis and establishes an antiviral state by inducing a variety of interferon-stimulated genes (ISGs). Notably, the induction of the ISGs by compound 1 was independent of the production of type 1 interferons. The antiviral activity of compound 1 was cell type dependent with a robust effect observed in human cell lines and no observed antiviral effect in mouse cell lines. Herein, we disclose tetrahydrobenzothiazole compound 1 as a novel lead for the development of a broad-spectrum, antiviral therapeutic and as a molecular probe to study the mechanism of the induction of ISGs that are independent of type 1 interferons.
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12

Žigrayová, Dominika, Veronika Mikušová, and Peter Mikuš. "Advances in Antiviral Delivery Systems and Chitosan-Based Polymeric and Nanoparticulate Antivirals and Antiviral Carriers." Viruses 15, no. 3 (February 28, 2023): 647. http://dx.doi.org/10.3390/v15030647.

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Current antiviral therapy research is focused on developing dosage forms that enable highly effective drug delivery, providing a selective effect in the organism, lower risk of adverse effects, a lower dose of active pharmaceutical ingredients, and minimal toxicity. In this article, antiviral drugs and the mechanisms of their action are summarized at the beginning as a prerequisite background to develop relevant drug delivery/carrier systems for them, classified and briefly discussed subsequently. Many of the recent studies aim at different types of synthetic, semisynthetic, and natural polymers serving as a favorable matrix for the antiviral drug carrier. Besides a wider view of different antiviral delivery systems, this review focuses on advances in antiviral drug delivery systems based on chitosan (CS) and derivatized CS carriers. CS and its derivatives are evaluated concerning methods of their preparation, their basic characteristics and properties, approaches to the incorporation of an antiviral drug in the CS polymer as well as CS nanoparticulate systems, and their recent biomedical applications in the context of actual antiviral therapy. The degree of development (i.e., research study, in vitro/ex vivo/in vivo preclinical testing), as well as benefits and limitations of CS polymer and CS nanoparticulate drug delivery systems, are reported for particular viral diseases and corresponding antivirotics.
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13

İNCE KÖSE, Tuğçe, and Ayşe Mine GENÇLER ÖZKAN. "ANTIVIRAL HERBS." Ankara Universitesi Eczacilik Fakultesi Dergisi 46, no. 2 (May 29, 2022): 505–22. http://dx.doi.org/10.33483/jfpau.1057473.

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Objective: Viruses are agents that can infect all kinds of living organisms, and the most important hosts are humans, animals, plants, bacteria and fungi. Viral diseases are responsible for serious morbidity and mortality worldwide, are a major threat to public health, and remain a major problem worldwide. The recently prominent Coronaviruses (CoVs) within this group belong to the Coronaviridae family, subfamily Coronavirinae, and are large (genome size 26−32 kb), enveloped, single-stranded ribonucleic acid (RNA ) viruses that can infect both animals and humans. The world has experienced three epidemics caused by betaCoVs in the last two decades: SARS in 2002−03, MERS in 2012, and COVID-19, first identified in 2019. COVID-19 continues to be our current health problem and studies on the subject continue.Result and Discussion: The term "antiviral agents" is defined in very broad terms as substances other than virus-containing vaccine or specific antibody that can produce a protective or therapeutic effect for the clearly detectable effect of the infected host.Nature has the potential to cure humanity's helplessness against viruses with many different plant species with strong antiviral effects. During the screening of plants with antiviral effects, focusing on plants used in folk medicine is of great importance in terms of maximizing the benefit to humanity - saving time and effort by dealing with valuable ancient knowledge on a scientific basis.In this review, viral diseases and the plants used in these diseases and determined to be effective are mentioned.
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Zhai, Xiaofeng, Shilei Wang, Mengyan Zhu, Wei He, Zhongzhou Pan, and Shuo Su. "Antiviral Effect of Lithium Chloride and Diammonium Glycyrrhizinate on Porcine Deltacoronavirus In Vitro." Pathogens 8, no. 3 (September 9, 2019): 144. http://dx.doi.org/10.3390/pathogens8030144.

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Porcine deltacoronavirus (PDCoV) is an emerging global swine virus that has a propensity for interspecies transmission. It was identified in Hong Kong in 2012. Given that neither specific antiviral drugs nor vaccines are available for newly emerging porcine deltacoronavirus, searching for effective antiviral drugs is a high priority. In this study, lithium chloride (LiCl) and diammonium glycyrrhizinate (DG), which are host-acting antivirals (HAAs), were tested against PDCoV. We found that LiCl and DG inhibited PDCoV replication in LLC-PK1 cells in a dose-dependent manner. The antiviral effects of LiCl and DG occurred at the early stage of PDCoV replication, and DG also inhibited virus attachment to the cells. Moreover, both drugs inhibited PDCoV-induced apoptosis in LLC-PK1 cells. This study suggests LiCl and DG as new drugs for the treatment of PDCoV infection.
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Rusu, Aura, Eliza-Mihaela Arbănaşi, Ioana-Andreea Lungu, and Octavia-Laura Moldovan. "Perspectives on Antiviral Drugs Development in the Treatment of COVID-19." Acta Biologica Marisiensis 4, no. 1 (June 1, 2021): 44–59. http://dx.doi.org/10.2478/abmj-2021-0005.

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Abstract The main objective of this review is to highlight the urgent development of new antiviral drugs against SARS-CoV-2 in the context of the coronavirus pandemic. Antiviral medication against SARS-CoV-2 comprises only remdesivir as an approved drug. Scientists are making considerable efforts to identify other effective antivirals. Investments into the de novo design of new drugs against the SARS-CoV-2 virus are few. Molnupiravir proved to be effective against the SARS-CoV-2 virus and is very close to approval. Pfizer’s two new compounds (PF-07321332, oral administration and PF-07304814, systemic administration) are in the early stages of development. Two types of methods are preferred to discover new antivirals in a short period. Repositioning of approved drugs for antiviral effect conducted to some clinical results for favipiravir, lopinavir/ritonavir, danoprevir/ritonavir, umifenovir, hydroxychloroquine, camostat and nafamostat. Virtual screening of known molecules’ libraries indicated several compounds that were tested or are being tested in clinical trials. In conclusion, only a few innovative antiviral molecules are in various stages of development. However, the repositioning of many known compounds is being studied, including using virtual screening. The pharmaceutical industry is adapting and reinventing itself so that humanity can face a new pandemic in the future.
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Carrasco, Luis R., Vernon J. Lee, Mark I. Chen, David B. Matchar, James P. Thompson, and Alex R. Cook. "Strategies for antiviral stockpiling for future influenza pandemics: a global epidemic-economic perspective." Journal of The Royal Society Interface 8, no. 62 (February 4, 2011): 1307–13. http://dx.doi.org/10.1098/rsif.2010.0715.

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Influenza pandemics present a global threat owing to their potential mortality and substantial economic impacts. Stockpiling antiviral drugs to manage a pandemic is an effective strategy to offset their negative impacts; however, little is known about the long-term optimal size of the stockpile under uncertainty and the characteristics of different countries. Using an epidemic–economic model we studied the effect on total mortality and costs of antiviral stockpile sizes for Brazil, China, Guatemala, India, Indonesia, New Zealand, Singapore, the UK, the USA and Zimbabwe. In the model, antivirals stockpiling considerably reduced mortality. There was greater potential avoidance of expected costs in the higher resourced countries (e.g. from $55 billion to $27 billion over a 30 year time horizon for the USA) and large avoidance of fatalities in those less resourced (e.g. from 11.4 to 2.3 million in Indonesia). Under perfect allocation, higher resourced countries should aim to store antiviral stockpiles able to cover at least 15 per cent of their population, rising to 25 per cent with 30 per cent misallocation, to minimize fatalities and economic costs. Stockpiling is estimated not to be cost-effective for two-thirds of the world's population under current antivirals pricing. Lower prices and international cooperation are necessary to make the life-saving potential of antivirals cost-effective in resource-limited countries.
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17

Alonzi, Dominic S., Kathryn A. Scott, Raymond A. Dwek, and Nicole Zitzmann. "Iminosugar antivirals: the therapeutic sweet spot." Biochemical Society Transactions 45, no. 2 (April 13, 2017): 571–82. http://dx.doi.org/10.1042/bst20160182.

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Many viruses require the host endoplasmic reticulum protein-folding machinery in order to correctly fold one or more of their glycoproteins. Iminosugars with glucose stereochemistry target the glucosidases which are key for entry into the glycoprotein folding cycle. Viral glycoproteins are thus prevented from interacting with the protein-folding machinery leading to misfolding and an antiviral effect against a wide range of different viral families. As iminosugars target host enzymes, they should be refractory to mutations in the virus. Iminosugars therefore have great potential for development as broad-spectrum antiviral therapeutics. We outline the mechanism giving rise to the antiviral activity of iminosugars, the current progress in the development of iminosugar antivirals and future prospects for this field.
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Rivera-Serrano, Bianca Vianey, Sandy Lucero Cabanillas-Salcido, Carlos Daniel Cordero-Rivera, Ricardo Jiménez-Camacho, Claudia Desiree Norzagaray-Valenzuela, Loranda Calderón-Zamora, Luis Adrián De Jesús-González, et al. "Antiviral Effect of Microalgae Phaeodactylum tricornutum Protein Hydrolysates against Dengue Virus Serotype 2." Marine Drugs 22, no. 8 (August 14, 2024): 369. http://dx.doi.org/10.3390/md22080369.

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Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10–30 kDa peptide fraction, at 150 and 300 μg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.
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Tican, Andreea, Mihaela Cioloca, Maria Ștefan, Carmen Bădărău, and Monica Popa. "Effect of Antiviral Compounds on the Regeneration of Potato Meristems." Romanian Agricultural Research 38 (2021): 117–22. http://dx.doi.org/10.59665/rar3812.

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The aim of this research was to determine the phytotoxic effect of chemotherapeutic products over meristematic explants from two potato Romanian varieties: Marvis and Castrum. Potato meristems were cultured on nutritive medium containing four virocid chemicals: ribavirin, 5-bromouracil, 2-thiouracil and acyclovir in three concentrations (0, 15, 30 mg/l). Meristems development varied for tested antiviral agents and was decreased with increasing in concentration of antiviral products (from 0 to 30 mg/l). Antiviral products with high concentration (30 mg/l) had a negative effect on regeneration. By using 5-bromouracil the highest regeneration rate was observed (for 15 mg/l and 30 mg/l), compared to the other antiviral substances, with the same concentrations. Another chemotherapeutic 2-thiouracil exhibited phytotoxicity and reduced meristems regeneration. The lowest percentage of regeneration was registered by using of 15 mg/l 2-thiouracil compared to the other antivirals, at the same concentration. Percent of meristems regeneration was very low for ribavirin and 2-thiouracil at 30 mg/l concentrations (40%). For Castrum variety 5-bromouracil is distinguished by obtaining a very significant positive difference (19.17% regenerated meristems), but the virocid 2-thiouracil is at the opposite pole, inhibiting the regeneration of explants, with a very significant negative difference (-14.17% developed explants).
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Gudima, Georgii, Ilya Kofiadi, Igor Shilovskiy, Dmitry Kudlay, and Musa Khaitov. "Antiviral Therapy of COVID-19." International Journal of Molecular Sciences 24, no. 10 (May 16, 2023): 8867. http://dx.doi.org/10.3390/ijms24108867.

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Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.
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Mihai, Maria Elena, Alina Elena Ivanciuc, Carmen Maria Cherciu, Grigore Mihăescu, and Mihaela Lazăr. "Monitoring the sensitivity of influenza viruses to oseltamivir, in Romania, from 2016 to 2023." Revista Romana de Medicina de Laborator 32, no. 2 (April 1, 2024): 163–70. http://dx.doi.org/10.2478/rrlm-2024-0010.

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Abstract Introduction: influenza is an acute viral disease caused by infection of the upper respiratory tract - difficult to control, which affects a large part of the population. Neuraminidase inhibitors (NAIs), such as oseltamivir and zanamivir, are the antiviral drugs utilized in Romania for the treatment of respiratory infections caused by the influenza viruses. The objective of the study is to monitor and analyze influenza viruses circulating in Romania, in terms of their susceptibility to oseltamivir, with the aim of signalling the emergence of viral strains resistant to antivirals. Methods: The phenotypic method was performed to evaluate the inhibitory effect of oseltamivir on the neuraminidase enzyme activity of influenza viruses. Genotypic methods (SNP-based assays or sequencing of neuraminidase/whole genome) were used for detecting amino acid substitutions associated with influenza antiviral resistance. The study period is from 2016 to 2023. Results: from the total number of influenza viruses isolated during the period (833 isolated), 670 strains were characterized antigenically and genetically, and the phenotypic susceptibility to antivirals was performed for 245 isolated viral strains. According to WHO criteria categories antiviral susceptibility based on IC50 data, none of the test results indicated reduced or highly reduced inhibition by oseltamivir. Conclusion: This monitoring, carried out in the National Influenza Center Romania - Cantacuzino NMMIRD, is extremely important to maintain effective flu control and further development of other antiviral agents.
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Patel-Dovlatabadi, Payal. "Factors associated with physicians' prescribing behavior for treatment of influenza in the USA." International Journal of Pharmaceutical and Healthcare Marketing 8, no. 1 (April 1, 2014): 27–46. http://dx.doi.org/10.1108/ijphm-01-2013-0002.

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Purpose – The aim of this paper is to identify factors (i.e. age, gender, ethnicity, type of medical facility, geographical location, etc.) associated with physicians' prescribing behavior when treating influenza in the USA. The study aims to examine why the number of antiviral prescriptions remains substandard. Design/methodology/approach – Data were obtained from the National Ambulatory Medical Care Survey for each influenza season between the years of 2005-2008. Bivariate analyses and two models of multivariate logistic regression analyses (one with no fixed effect and the other including year as a fixed effect) were used to analyze the data. Findings – The results from this study revealed that among family practice physicians, 40.5 percent prescribed antiviral medications to patients presenting with influenza while 59.5 percent prescribed another form of medication. Antibiotics comprised 41.3 percent of the prescriptions for treatment of influenza. Multivariable logistic regression analyses revealed that race (White; p=0.023), type of health setting (private solo/group practice; p=0.041), employment status (owner; p=0.046), and metropolitan location (metropolitan statistical area; p=0.032) were all significantly associated with prescribing antivirals. Patients' expected source of payment (private insurance) and geographical location (Midwest) of health facility were marginally associated with prescribing antivirals. Originality/value – By identifying factors associated with physicians' prescribing practices of antiviral medications, a more timely diagnosis and treatment of influenza can occur. Efforts should be targeted to improve physician education and awareness of the illness. Interventions may be implemented to improve the prescribing of antiviral medications and potentially inappropriate prescribing.
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Mohamed, Fakry F., Darisuren Anhlan, Michael Schöfbänker, André Schreiber, Nica Classen, Andreas Hensel, Georg Hempel, et al. "Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2." Pharmaceuticals 15, no. 5 (April 25, 2022): 530. http://dx.doi.org/10.3390/ph15050530.

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For almost two years, the COVID-19 pandemic has constituted a major challenge to human health, particularly due to the lack of efficient antivirals to be used against the virus during routine treatment interventions. Multiple treatment options have been investigated for their potential inhibitory effect on SARS-CoV-2. Natural products, such as plant extracts, may be a promising option, as they have shown an antiviral activity against other viruses in the past. Here, a quantified extract of Hypericum perforatum was tested and found to possess a potent antiviral activity against SARS-CoV-2. The antiviral potency of the extract could be attributed to the naphtodianthrones hypericin and pseudohypericin, in contrast to other tested ingredients of the plant material, which did not show any antiviral activity. Hypericum perforatum and its main active ingredient hypericin were also effective against different SARS-CoV-2 variants (Alpha, Beta, Delta, and Omicron). Concerning its mechanism of action, evidence was obtained that Hypericum perforatum and hypericin may hold a direct virus-blocking effect against SARS-CoV-2 virus particles. Taken together, the presented data clearly emphasize the promising antiviral activity of Hypericum perforatum and its active ingredients against SARS-CoV-2 infections.
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Mohamed, Fakry F., Darisuren Anhlan, Michael Schöfbänker, André Schreiber, Nica Classen, Andreas Hensel, Georg Hempel, et al. "Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2." Pharmaceuticals 15, no. 5 (April 25, 2022): 530. http://dx.doi.org/10.3390/ph15050530.

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For almost two years, the COVID-19 pandemic has constituted a major challenge to human health, particularly due to the lack of efficient antivirals to be used against the virus during routine treatment interventions. Multiple treatment options have been investigated for their potential inhibitory effect on SARS-CoV-2. Natural products, such as plant extracts, may be a promising option, as they have shown an antiviral activity against other viruses in the past. Here, a quantified extract of Hypericum perforatum was tested and found to possess a potent antiviral activity against SARS-CoV-2. The antiviral potency of the extract could be attributed to the naphtodianthrones hypericin and pseudohypericin, in contrast to other tested ingredients of the plant material, which did not show any antiviral activity. Hypericum perforatum and its main active ingredient hypericin were also effective against different SARS-CoV-2 variants (Alpha, Beta, Delta, and Omicron). Concerning its mechanism of action, evidence was obtained that Hypericum perforatum and hypericin may hold a direct virus-blocking effect against SARS-CoV-2 virus particles. Taken together, the presented data clearly emphasize the promising antiviral activity of Hypericum perforatum and its active ingredients against SARS-CoV-2 infections.
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Mohamed, Fakry F., Darisuren Anhlan, Michael Schöfbänker, André Schreiber, Nica Classen, Andreas Hensel, Georg Hempel, et al. "Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2." Pharmaceuticals 15, no. 5 (April 25, 2022): 530. http://dx.doi.org/10.3390/ph15050530.

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For almost two years, the COVID-19 pandemic has constituted a major challenge to human health, particularly due to the lack of efficient antivirals to be used against the virus during routine treatment interventions. Multiple treatment options have been investigated for their potential inhibitory effect on SARS-CoV-2. Natural products, such as plant extracts, may be a promising option, as they have shown an antiviral activity against other viruses in the past. Here, a quantified extract of Hypericum perforatum was tested and found to possess a potent antiviral activity against SARS-CoV-2. The antiviral potency of the extract could be attributed to the naphtodianthrones hypericin and pseudohypericin, in contrast to other tested ingredients of the plant material, which did not show any antiviral activity. Hypericum perforatum and its main active ingredient hypericin were also effective against different SARS-CoV-2 variants (Alpha, Beta, Delta, and Omicron). Concerning its mechanism of action, evidence was obtained that Hypericum perforatum and hypericin may hold a direct virus-blocking effect against SARS-CoV-2 virus particles. Taken together, the presented data clearly emphasize the promising antiviral activity of Hypericum perforatum and its active ingredients against SARS-CoV-2 infections.
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Goldberg, M., L. S. Belkowski, and B. R. Bloom. "Regulation of macrophage growth and antiviral activity by interferon-gamma." Journal of Cell Biology 109, no. 3 (September 1, 1989): 1331–40. http://dx.doi.org/10.1083/jcb.109.3.1331.

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Interferons, in addition to their antiviral activity, induce a multiplicity of effects on different cell types. Interferon (IFN)-gamma exerts a unique regulatory effect on cells of the mononuclear phagocyte lineage. To investigate whether the antiviral and antiproliferative effects of IFN-gamma in macrophages can be genetically dissociated, and whether IFN-alpha and IFN-gamma use the same cellular signals and/or effector mechanisms to achieve their biologic effects, we have derived a series of somatic cell genetic variants resistant to the antiproliferative and/or antiviral activities of IFN-gamma. Two different classes of variants were found: those resistant to the antiproliferative and antiviral effects of IFN-gamma against vesicular stomatitis virus (VSV) and those resistant to the antiproliferative effect, but protected against VSV and encephalomyocarditis virus (EMCV) lysis by IFN-gamma. In addition, a third class of mutants was obtained that was susceptible to the growth inhibitory activity, but resistant to the antiviral activity of IFN-gamma. Analysis of these mutants has provided several insights regarding the regulatory mechanisms of IFN-gamma and IFN-alpha on the murine macrophage cell lines. The antiproliferative activity of IFN-gamma on these cells, in contrast to that of IFN-alpha, is mediated by a cAMP-independent pathway. The antiproliferative and antiviral activities of IFN-gamma were genetically dissociated. Variants were obtained that are growth resistant but antivirally protected, or are growth inhibited but not antivirally protected against VSV or EMCV. The genetic analysis indicated that IFN-alpha and IFN-gamma regulate the induction of the dsRNA-dependent P1/eIF-2 alpha protein kinase and 2',5'-oligoadenylate synthetase enzymatic activities via different pathways. Finally, a unique macrophage mutant was obtained that was protected by IFN-gamma against infection by VSV, but not EMCV, suggesting that antiviral mechanisms involved in protection against these different types of RNA viruses must be distinct at some level.
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Mutimer, David J., and Anna Lok. "Management of HBV- and HCV-induced end stage liver disease." Gut 61, Suppl 1 (April 12, 2012): i59—i67. http://dx.doi.org/10.1136/gutjnl-2012-302076.

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Hepatitis B and hepatitis C infections are important causes of end-stage liver disease and primary liver cancer. Successful antiviral treatment prior to the development of cirrhosis will prevent most of the morbidity and mortality associated with those infections. This can be achieved for a high proportion of patients. However, many patients present with end-stage liver disease and ongoing and clinically significant viral replication. Antiviral treatment of HBV can effect recovery of liver function and restores many patients to a state of well compensated cirrhosis. The antiviral treatment of end-stage HCV poses much greater challenges. Interferon remains an essential element of HCV antiviral treatment, but has reduced efficacy and significant toxicity at this stage of cirrhosis. Though yet to be evaluated in the setting of advanced liver disease, the development of direct acting antivirals for HCV offers hope for improved outcomes at this stage of cirrhosis.
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Tvrzová, Ludmila, Anna Bláhová, Jakub Fojt, Hana Doubková, and Jiří Procházka. "ANTIVIRAL TEXTILES AND ANTIVIRAL ACTIVITY TESTING - THE USE OF BACTERIOPHAGE SURROGATE FOR ANTIVIRAL ACTIVITY TESTING." Fibres and Textiles 31, no. 2 (September 2024): 28–34. http://dx.doi.org/10.15240/tul/008/2024-2-004.

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The risk of dissemination of highly contagious viral diseases (as COVID-19, Ebola) led in the increasing need to develop functional textiles and surfaces with antiviral effect. Antiviral textiles are designed to reduce the viability and infectivity of viruses on their surfaces and by this way to reduce the cases of infection (including re-infection or cross-infection with contaminated textiles). Different antiviral agents and diverse techniques of their application are used for functionalized textiles manufacturing. The most often used antivirals are metallic and ionic silver and copper, iron oxide, quaternary ammonium salts. The aim of the process is to prepare textiles with long-term durable finishing effective in viral activity inhibition. The basic step of functionalized antiviral textiles development is antiviral effectivity testing. The safe method of testing with the use of Phi6 bacteriophage, SARS-CoV-2 and Ebola virus surrogate, was modified for antiviral textiles testing. The samples of textiles with antiviral finishing were tested by the bacteriophage-based method and excellent antiviral activity was detected for all tested materials. The woven cotton was used as reference untreated material, the different textile cotton structures with similar square weight were compared and no statistically significant difference was found between the resulting antiviral efficacy values. A simple and quickly feasible screening method for determining the antiviral properties of textiles, especially with leaching-type of treatment, was also designed and tested.
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Tsuge, Masataka. "Are Humanized Mouse Models Useful for Basic Research of Hepatocarcinogenesis through Chronic Hepatitis B Virus Infection?" Viruses 13, no. 10 (September 24, 2021): 1920. http://dx.doi.org/10.3390/v13101920.

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Chronic hepatitis B virus (HBV) infection is a global health problem that can lead to liver dysfunction, including liver cirrhosis and hepatocellular carcinoma (HCC). Current antiviral therapies can control viral replication in patients with chronic HBV infection; however, there is a risk of HCC development. HBV-related proteins may be produced in hepatocytes regardless of antiviral therapies and influence intracellular metabolism and signaling pathways, resulting in liver carcinogenesis. To understand the mechanisms of liver carcinogenesis, the effect of HBV infection in human hepatocytes should be analyzed. HBV infects human hepatocytes through transfer to the sodium taurocholate co-transporting polypeptide (NTCP). Although the NTCP is expressed on the hepatocyte surface in several animals, including mice, HBV infection is limited to human primates. Due to this species-specific liver tropism, suitable animal models for analyzing HBV replication and developing antivirals have been lacking since the discovery of the virus. Recently, a humanized mouse model carrying human hepatocytes in the liver was developed based on several immunodeficient mice; this is useful for analyzing the HBV life cycle, antiviral effects of existing/novel antivirals, and intracellular signaling pathways under HBV infection. Herein, the usefulness of human hepatocyte chimeric mouse models in the analysis of HBV-associated hepatocarcinogenesis is discussed.
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Kabir, Muhammad Ashraful, Baishakhi Islam, Tasnim Rahman, Tamanna Jannat, Jesmin Zahan Tuli, and Abdullah Al Faroque. "Current Trend of Prescribing Anticoagulant and Antiviral Drugs in the Treatment of COVID- 19 Patients in a Corona Dedicated Hospital in Khulna." Mediscope 10, no. 1 (April 11, 2023): 10–16. http://dx.doi.org/10.3329/mediscope.v10i1.65402.

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Background: Thrombo-embolic incidence secondary to COVID-19 with increased mortality rate has become a global concern. Anticoagulants are widely used to prevent mortality. On the other hand, antiviral therapy has a potential effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aims & objectives: This study aims to assess the use pattern of anticoagulant and antiviral drugs against COVID-19. Methods: This is an observational cross-sectional study where two hundred COVID-19-positive patients of both sexes and different age groups who received anticoagulants and antivirals were recruited. All data were compiled in a Microsoft excel spreadsheet. Results were expressed in frequency & percentage. Results: Out of 200 patients, there were 115 males (57.5%) & 85 females (42.5%); the majority (56%) belonged to the age group between 30 to 60 years. Clinically, patients were categorized into mild (25%), moderate (32%), severe (37.5%), and critical (5.5%) cases. In this study, 88% of patients received low molecular weight heparin (enoxaparin) in a prophylactic dose and 12% of patients received in a therapeutic dose. Among the antivirals, remdesivir (84%) followed by favipiravir (16%) were the most commonly prescribed drugs. Conclusion: Anticoagulant (enoxaparin) and antiviral (remdesivir) drugs are frequently prescribed in the treatment of COVID-19 patients. Mediscope 2023;10(1):10-16
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Sullender, Meagan E., Linley Pierce, Rachel Rodgers, Lawrence Schriefer, Bria F. Dunlap, John G. Doench, Robert C. Orchard, and Megan T. Baldridge. "TRIMming viral infection: identification and characterization of the novel antiviral TRIM7." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 20.35. http://dx.doi.org/10.4049/jimmunol.206.supp.20.35.

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Abstract Noroviruses (NoVs) are the leading cause of acute viral gastroenteritis worldwide, causing up to 700 million infections and 200,000 deaths annually, and treatment is limited to supportive care as there are currently no targeted antivirals nor vaccines against NoVs. Therefore, it is critical to discover novel antivirals and develop targeted interventions in order to improve outcomes. Here we have used a novel genome-wide CRISPR activation screening approach to identify host genes that can inhibit murine norovirus (MNoV) infection or replication. A substantial number of high scoring gene candidates acted in interferon and immune regulation signaling networks, but several were not previously associated with antiviral activity or immunity. TRIM7, the strongest screen hit, was a little studied E3 ubiquitin ligase associated with metabolism and some cancers, yet its expression served as a powerful antiviral in an MNoV-infected cell. Since our initial screen, TRIM7 has begun to emerge as a strategic player in both positive and negative regulation of the innate immune response during infection. We have since characterized the antiviral mechanism of action of TRIM7 against MNoV in vitro, and have found TRIM7 to be acting early in the viral life cycle to limit viral protein production. Co-immunoprecipitation and in vitro viral evolution experiments have identified MNoV NS6 (viral protease) and NS7 (RNA-dependent RNA polymerase) as important targets of the antiviral activity of TRIM7, and also point to key residues of interest associated with MNoV resistance to TRIM7. Finally, we have investigated the relevance of TRIM7 during in vivo infection using knock-in mouse lines to determine tissue specificity and potency of the antiviral effect.
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Hu, Zhao X., Yi N. Ye, Wei G. Wu, Xu J. Liang, Qi W. Wu, Ao Zhang, Xing R. Zheng, Zhi L. Gao, Liang Peng, and Chan Xie. "Real-Life State of Anti-Hepatitis B Virus Drug Choice in Child-Bearing Age Male Patients and Effect on Fertility and Fetal Safety." Canadian Journal of Gastroenterology and Hepatology 2019 (April 1, 2019): 1–8. http://dx.doi.org/10.1155/2019/9703907.

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Research on effects of anti-hepatitis B virus (HBV) nucleoside analogs on male fertility and birth defects is limited and safety of nucleoside analogs in pregnancy is still a concern. Chronic hepatitis B (CHB) patients in Guangdong province were surveyed using a structured questionnaire. We collected data including medication type, fertility, and birth defects. Moreover, a survey of the knowledge of antiviral nucleoside analogs safety in fertility of male patients was conducted among physicians nationwide. Semen samples of 30 patients were collected. We screened 1050 HBV-positive male patients. Reasons for not receiving antivirals in 150 patients were “did not meet criteria for antiviral therapy,” fertility, and financial. Furthermore, 900 participants received antivirals (85.71%, 900/1050), including 792 patients with children and 15.15% (120/792) took anti-HBV treatment when preparing for pregnancy. Based on whether they received antiviral therapy during conception or not, we divided patients into two groups. In the child-bearing age group, 88.33% (106/120) of patients received telbivudine (LDT), whereas the other group mainly received entecavir (ETV) (87.20%, 586/672). No significant difference occurred in birth defect incidence rates between both groups. Furthermore, 558 physicians completed questionnaires. Reasons that influenced drug selection were “patient’s condition,” “fertility demand,” “financial condition,” and “compliance.” Telbivudine was the first-choice drug (32.80%, 183/558) while tenofovir (TDF) was the second (2.69%, 15/558). Additionally, 61.47% of physicians considered telbivudine or tenofovir as the first choice for male patients who met antiviral criteria, whereas 19% suggested delayed therapy and follow-up until childbirth. No significant changes occurred in semen volume, concentration, mobility, and percentage before and after administration of anti-HBV nucleoside analogs, which did not affect male fertility and birth defect incidence while the desire for pregnancy influenced drug selection and timing of administration. Further research on the effects of analogs on male fertility and fetal safety is required.
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Pelz, Lars, Elena Piagnani, Patrick Marsall, Nancy Wynserski, Marc Dominique Hein, Pavel Marichal-Gallardo, Sascha Young Kupke, and Udo Reichl. "Broad-Spectrum Antiviral Activity of Influenza A Defective Interfering Particles against Respiratory Syncytial, Yellow Fever, and Zika Virus Replication In Vitro." Viruses 15, no. 9 (September 4, 2023): 1872. http://dx.doi.org/10.3390/v15091872.

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New broadly acting and readily available antiviral agents are needed to combat existing and emerging viruses. Defective interfering particles (DIPs) of influenza A virus (IAV) are regarded as promising options for the prevention and treatment of IAV infections. Interestingly, IAV DIPs also inhibit unrelated viral infections by stimulating antiviral innate immunity. Here, we tested the ability of IAV DIPs to suppress respiratory syncytial, yellow fever and Zika virus infections in vitro. In human lung (A549) cells, IAV DIP co-infection inhibited the replication and spread of all three viruses. In contrast, we observed no antiviral activity in Vero cells, which are deficient in the production of interferon (IFN), demonstrating its importance for the antiviral effect. Further, in A549 cells, we observed an enhanced type-I and type-III IFN response upon co-infection that appears to explain the antiviral potential of IAV DIPs. Finally, a lack of antiviral activity in the presence of the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib was detected. This revealed a dependency of the antiviral activity on the JAK/signal transducers and activators of transcription (STAT) signaling pathway. Overall, this study supports the notion that IAV DIPs may be used as broad-spectrum antivirals to treat infections with a variety of IFN-sensitive viruses, particularly respiratory viruses.
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Jang, Jeong Won, Sun Hong Yoo, Hee Chul Nam, Bo Hyun Jang, Pil Soo Sung, Sung, Won Lee, Jung Hyun Kwon, et al. "Association of Prophylactic Anti–Hepatitis B Virus Therapy With Improved Long-term Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Therapy." Clinical Infectious Diseases 71, no. 3 (September 1, 2019): 546–55. http://dx.doi.org/10.1093/cid/ciz860.

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Abstract Background The effect of prophylactic antiviral therapy (AVT) on survival of patients with hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine whether prophylactic AVT could improve long-term survival in patients undergoing transarterial chemotherapy (TAC). Methods Between 2002 and 2016, 2860 newly diagnosed HBV-related patients with HCC treated with TAC were screened to analyze 2 groups based on prophylactic use of antivirals. Treatment effects were analyzed using propensity score (PS) matching (1:1) separately for the entire cohort and each subgroup. The primary endpoint was overall survival. Results A total of 1547 patients met the inclusion criteria and 1084 were PS matched for the 2 groups. Median follow-up duration was 16.55 months. In the entire unmatched cohort, patients receiving prophylactic AVT survived significantly longer than those who did not. Among AVT-untreated patients, baseline high viremia and HBV reactivation during treatment were significantly associated with shorter survival. Regarding types of antivirals, survival was significantly longer for patients receiving high-potency antivirals than those receiving low-potency antivirals. Survival differed with antiviral response. In the PS-matched cohort, the prophylactic AVT group survived significantly longer than the nonprophylactic group, irrespective of viral status or tumor stage. Prophylactic AVT remained an independent factor for survival. The association of prophylactic AVT with decreased risk of mortality persisted in patient subgroups after adjusting for baseline risk factors. Sensitivity analyses also confirmed estimated treatment effects. Conclusions Prophylactic AVT is associated with significantly improved long-term survival among patients undergoing TAC. High-potency antivirals are indicated for this approach. Hepatitis B virus–associated morbidity is a well-known complication during transarterial chemotherapy (TAC). Our large-scale study demonstrated that prophylactic therapy with high-potency antivirals provides a significantly better survival in TAC-treated patients, irrespective of baseline viremia status or tumor stage.
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Rabbani, M. A. G., Michael Ribaudo, Ju-Tao Guo, and Sailen Barik. "Identification of Interferon-Stimulated Gene Proteins That Inhibit Human Parainfluenza Virus Type 3." Journal of Virology 90, no. 24 (October 5, 2016): 11145–56. http://dx.doi.org/10.1128/jvi.01551-16.

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ABSTRACTA major arm of cellular innate immunity is type I interferon (IFN), represented by IFN-α and IFN-β. Type I IFN transcriptionally induces a large number of cellular genes, collectively known as IFN-stimulated gene (ISG) proteins, which act as antivirals. The IFIT (interferon-induced proteins with tetratricopeptide repeats) family proteins constitute a major subclass of ISG proteins and are characterized by multiple tetratricopeptide repeats (TPRs). In this study, we have interrogated IFIT proteins for the ability to inhibit the growth of human parainfluenza virus type 3 (PIV3), a nonsegmented negative-strand RNA virus of theParamyxoviridaefamily and a major cause of respiratory disease in children. We found that IFIT1 significantly inhibited PIV3, whereas IFIT2, IFIT3, and IFIT5 were less effective or not at all. In further screening a set of ISG proteins we discovered that several other such proteins also inhibited PIV3, including IFITM1, IDO (indoleamine 2,3-dioxygenase), PKR (protein kinase, RNA activated), and viperin (virus inhibitory protein, endoplasmic reticulum associated, interferon inducible)/Cig5. The antiviral effect of IDO, the enzyme that catalyzes the first step of tryptophan degradation, could be counteracted by tryptophan. These results advance our knowledge of diverse ISG proteins functioning as antivirals and may provide novel approaches against PIV3.IMPORTANCEThe innate immunity of the host, typified by interferon (IFN), is a major antiviral defense. IFN inhibits virus growth by inducing a large number of IFN-stimulated gene (ISG) proteins, several of which have been shown to have specific antiviral functions. Parainfluenza virus type 3 (PIV3) is major pathogen of children, and no reliable vaccine or specific antiviral against it currently exists. In this article, we report several ISG proteins that strongly inhibit PIV3 growth, the use of which may allow a better antiviral regimen targeting PIV3.
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Jousselin, Clément, Hugo Pliego-Cortés, Alexia Damour, Magali Garcia, Charles Bodet, Daniel Robledo, Nathalie Bourgougnon, and Nicolas Lévêque. "Anti-SARS-CoV-2 Activity of Polysaccharides Extracted from Halymenia floresii and Solieria chordalis (Rhodophyta)." Marine Drugs 21, no. 6 (June 6, 2023): 348. http://dx.doi.org/10.3390/md21060348.

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Even after hundreds of clinical trials, the search for new antivirals to treat COVID-19 is still relevant. Carrageenans are seaweed sulfated polysaccharides displaying antiviral activity against a wide range of respiratory viruses. The objective of this work was to study the antiviral properties of Halymenia floresii and Solieria chordalis carrageenans against SARS-CoV-2. Six polysaccharide fractions obtained from H. floresii and S. chordalis by Enzyme-Assisted Extraction (EAE) or Hot Water Extraction (HWE) were tested. The effect of carrageenan on viral replication was assessed during infection of human airway epithelial cells with a clinical strain of SARS-CoV-2. The addition of carrageenans at different times of the infection helped to determine their mechanism of antiviral action. The four polysaccharide fractions isolated from H. floresii displayed antiviral properties while the S. chordalis fractions did not. EAE-purified fractions caused a stronger reduction in viral RNA concentration. Their antiviral action is likely related to an inhibition of the virus attachment to the cell surface. This study confirms that carrageenans could be used as first-line treatment in the respiratory mucosa to inhibit the infection and transmission of SARS-CoV-2. Low production costs, low cytotoxicity, and a broad spectrum of antiviral properties constitute the main strengths of these natural molecules.
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Varbanov, Mihayl, Stéphanie Philippot, and Miguel A. González-Cardenete. "Anticoronavirus Evaluation of Antimicrobial Diterpenoids: Application of New Ferruginol Analogues." Viruses 15, no. 6 (June 9, 2023): 1342. http://dx.doi.org/10.3390/v15061342.

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The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in virus titer as well as the inhibition of a cytopathic effect. A toxicity prediction based on in silico analysis was also performed as well as an estimation of bioavailability. This work demonstrates the antimicrobial and specifically antiviral activity of two tested compounds, making these molecules interesting for the development of new antivirals.
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Bassetto, Marcella, Cecilia M. Cima, Mattia Basso, Martina Salerno, Frank Schwarze, Daniela Friese, Joachim J. Bugert, and Andrea Brancale. "Novel Nucleoside Analogues as Effective Antiviral Agents for Zika Virus Infections." Molecules 25, no. 20 (October 20, 2020): 4813. http://dx.doi.org/10.3390/molecules25204813.

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Previously considered a neglected flavivirus, Zika virus has recently emerged as a public health concern due to its ability to spread rapidly and cause severe neurological disorders, such as microcephaly in newborn babies from infected mothers, and Guillain-Barré syndrome in adults. Despite extensive efforts towards the identification of effective therapies, specific antivirals are still not available. As part of ongoing medicinal chemistry studies to identify new antiviral agents, we screened against Zika virus replication in vitro in a targeted internal library of small-molecule agents, comprising both nucleoside and non-nucleoside agents. Among the compounds evaluated, novel aryloxyphosphoramidate prodrugs of the nucleosides 2′-C-methyl-adenosine, 2-CMA, and 7-deaza-2′C-methyl-adenosine, 7-DMA, were found to significantly inhibit the virus-induced cytopathic effect in multiple relevant cell lines. In addition, one of these prodrugs exhibits a synergistic antiviral effect against Zika virus when applied in combination with an indirect antiviral agent, a l-dideoxy bicyclic pyrimidine nucleoside analogue, which potently inhibits vaccinia and measles viruses in vitro by targeting a host pathway. Our findings provide a solid basis for further development of an antiviral therapy for Zika virus infections, possibly exploiting a dual approach combining two different agents, one targeting the viral polymerase (direct-acting antiviral), the second targeting a host-directed autophagy mechanism.
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He, Buyuan, James T. Tran, and David Jesse Sanchez. "Manipulation of Type I Interferon Signaling by HIV and AIDS-Associated Viruses." Journal of Immunology Research 2019 (April 4, 2019): 1–10. http://dx.doi.org/10.1155/2019/8685312.

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Type I Interferons were first described for their profound antiviral abilities in cell culture and animal models, and later, they were translated into potent antiviral therapeutics. However, as additional studies into the function of Type I Interferons progressed, it was also seen that pathogenic viruses have coevolved to encode potent mechanisms allowing them to evade or suppress the impact of Type I Interferons on their replication. For chronic viral infections, such as HIV and many of the AIDS-associated viruses, including HTLV, HCV, KSHV, and EBV, the clinical efficacy of Type I Interferons is limited by these mechanisms. Here, we review some of the ways that HIV and AIDS-associated viruses thrive in Type I Interferon-rich environments via mechanisms that block the function of this important antiviral cytokine. Overall, a better understanding of these mechanisms creates avenues to better understand the innate immune response to these viruses as well as plan the development of antivirals that would allow the natural antiviral effect of Type I Interferons to manifest during these infections.
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Triamyanti, Vincentina Yenny, Rika Yulia, Fauna Herawati, and Abdul Kadir Jaelani. "EVALUASI PERSENTASI KESESUAIAN DENGAN PEDOMAN 3 PENGGUNAAN ANTIBIOTIK DAN ANTIVIRUS PADA PASIEN COVID-19 NON VENTILATOR DI RSUD BANGIL." MEDFARM: Jurnal Farmasi dan Kesehatan 11, no. 2 (December 28, 2022): 127–41. http://dx.doi.org/10.48191/medfarm.v11i2.94.

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Coronavirus (Covid-19) is an infectious disease caused by the SARS-CoV-2 virus. Most people infected with this virus develop mild to moderate respiratory illness and recover without requiring special treatment. However, people who are older and have comorbid will experience severe illness and require medical attention that can lead to death. The aimed of this study was to provide an overview of the evaluation of the use of antibiotics and antivirals in non-ventilated Covid-19 patients at Bangil Hospital. The method used is Defined Daily Dose (DDD/100 patient-days) and One Way ANOVA analysis. Based on the DDD/100 patient-days value, the most widely used antibiotic group was Moxifloxacin and the most common antiviral group was Remdesivir. Meanwhile, based on different tests on the use of antibiotics and antivirals, it is known that there is no significant difference between those who use antibiotics and do not use antibiotics and those who use antivirals without using antivirals. Thus it can be concluded that the use of antibiotics and antivirals has no effect on the patient's recovery rate.
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Kiki, Manal Jameel. "In Vitro Antiviral Potential, Antioxidant, and Chemical Composition of Clove (Syzygium aromaticum) Essential Oil." Molecules 28, no. 6 (March 7, 2023): 2421. http://dx.doi.org/10.3390/molecules28062421.

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Viral infections are spread all around the world. Although there are available therapies, their safety and effectiveness are constrained by their adverse effects and drug resistance. Therefore, new natural antivirals have been used such as essential oils, which are natural products with promising biological activity. Accordingly, the present study aimed to identify the components of clove (Syzygium aromaticum) essential oil (EOCa) and verify its antioxidant and antiviral activity. The oil was analyzed using GC/MS, and the antioxidant capacity was evaluated as a function of the radical scavenging activity. A plaque reduction test was used to measure the antiviral activity against herpes simplex virus (HSV-1), hepatitis A virus (HAV), and an adenovirus. GC/MS analysis confirmed the presence of eugenol as the main component (76.78%). Moreover, EOCa had powerful antioxidant activity with an IC50 of 50 µg/mL. The highest antiviral potential was found against HAV, with a selectivity index (SI) of 14.46, while showing poor selectivity toward HSV-1 with an SI value of 1.44. However, no relevant effect was detected against the adenovirus. The antiviral activity against HAV revealed that its effect was not related to host cytotoxicity. The findings imply that EOCa can be utilized to treat diseases caused by infections and free radicals.
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42

Shefer, Shai, Arthur Robin, Alexander Chemodanov, Mario Lebendiker, Robert Bostwick, Lynn Rasmussen, Michael Lishner, Michael Gozin, and Alexander Golberg. "Fighting SARS-CoV-2 with green seaweed Ulva sp. extract: extraction protocol predetermines crude ulvan extract anti-SARS-CoV-2 inhibition properties in in vitro Vero-E6 cells assay." PeerJ 9 (November 15, 2021): e12398. http://dx.doi.org/10.7717/peerj.12398.

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Due to the global COVID-19 pandemic, there is a need to screen for novel compounds with antiviral activity against SARS-COV-2. Here we compared chemical composition and the in vitro anti- SARS-COV-2 activity of two different Ulva sp. crude ulvan extracts: one obtained by an HCl-based and another one by ammonium oxalate-based (AOx) extraction protocols. The composition of the crude extracts was analyzed and their antiviral activity was assessed in a cytopathic effect reduction assay using Vero E6 cells. We show that the extraction protocols have a significant impact on the chemical composition, anti- SARS-COV-2 activity, and cytotoxicity of these ulvan extracts. The ulvan extract based on the AOx protocol had a higher average molecular weight, higher charge, and 11.3-fold higher antiviral activity than HCl-based extract. Our results strongly suggest that further bioassay-guided investigation into bioactivity of compounds found in Ulva sp. ulvan extracts could lead to the discovery of novel anti-SARS-CoV-2 antivirals.
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43

Masmoudi, Fatma, Nanci Santos-Ferreira, Dasja Pajkrt, Katja C. Wolthers, Jeroen DeGroot, Maria L. H. Vlaming, Joana Rocha-Pereira, and Ludovico Buti. "Evaluation of 3D Human Intestinal Organoids as a Platform for EV-A71 Antiviral Drug Discovery." Cells 12, no. 8 (April 12, 2023): 1138. http://dx.doi.org/10.3390/cells12081138.

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Enteroviruses are a leading cause of upper respiratory tract, gastrointestinal, and neurological infections. Management of enterovirus-related diseases has been hindered by the lack of specific antiviral treatment. The pre-clinical and clinical development of such antivirals has been challenging, calling for novel model systems and strategies to identify suitable pre-clinical candidates. Organoids represent a new and outstanding opportunity to test antiviral agents in a more physiologically relevant system. However, dedicated studies addressing the validation and direct comparison of organoids versus commonly used cell lines are lacking. Here, we described the use of human small intestinal organoids (HIOs) as a model to study antiviral treatment against human enterovirus 71 (EV-A71) infection and compared this model to EV-A71-infected RD cells. We used reference antiviral compounds such as enviroxime, rupintrivir, and 2′-C-methylcytidine (2′CMC) to assess their effects on cell viability, virus-induced cytopathic effect, and viral RNA yield in EV-A71-infected HIOs and cell line. The results indicated a difference in the activity of the tested compounds between the two models, with HIOs being more sensitive to infection and drug treatment. In conclusion, the outcome reveals the value added by using the organoid model in virus and antiviral studies.
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44

Carangio, A., S. Srinivasan, C. McGuigan, G. Andrei, R. Snoeck, E. De Clercq, and J. Balzarini. "Bicyclic Nucleoside Inhibitors of Varicella-Zoster Virus: Effect of Terminal Aryl Substitution in the Side-Chain." Antiviral Chemistry and Chemotherapy 13, no. 5 (October 2002): 263–71. http://dx.doi.org/10.1177/095632020201300501.

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We have previously reported the discovery and preliminary structure-activity relationships of a new class of inhibitors of varicella-zoster virus (VZV). These novel furanopyrimidine nucleosides bear unusual bicyclic base moieties and exhibit complete specificity for VZV. Limited in vitro cytotoxicity has been detected and the bicyclic nucleosides are now well established as a new family of potent antivirals. Our initial studies revealed an absolute requirement of a long alkyl side-chain, with an optimal chain length of C8-C10, for antiviral activity. Following further studies, we recently reported a significant enhancement of both antiviral potency and selectivity by the inclusion of a phenyl group within the alkyl side-chain of these compounds. The new lead p-alkylphenyl analogues displayed EC50 values below 1 nM versus VZV and selectivity index values >1000000. We herein report the synthesis and characterization of a further series of alkylaryl analogues bearing terminal phenyl groups with varying n-alkyl side-chain lengths. Synthesis of the target bicyclic systems involved the Pd-catalysed coupling of terminal acetylenes with 5-iodo-2′-deoxyuridine to give intermediate 5-alkynyl nucleosides which were then cyclized in the presence of copper (I) iodide. The current compounds display excellent selectivity for VZV with no detectable in vitro cytotoxicity but despite being chemically isomeric with the previous lead p-alkylphenyl analogues, the compounds reported herein exhibit only moderate antiviral activities. A possible correlation between antiviral activity and conformational freedom of the side-chain is discussed.
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45

Alhumaid, Saad, Abbas Al Mutair, Zainab Al Alawi, Naif Alhmeed, Abdul Rehman Zia Zaidi, and Mansour Tobaiqy. "Efficacy and Safety of Lopinavir/Ritonavir for Treatment of COVID-19: A Systematic Review and Meta-Analysis." Tropical Medicine and Infectious Disease 5, no. 4 (November 28, 2020): 180. http://dx.doi.org/10.3390/tropicalmed5040180.

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(Background) Lopinavir-ritonavir (LPV/RTV) is a human immunodeficiency virus (HIV) antiviral combination that has been considered for the treatment of COVID-19 disease. (Aim) This systematic review aimed to assess the efficacy and safety of LPV/RTV in COVID-19 patients in the published research. (Methods) A protocol was developed based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Articles were selected for review from 8 electronic databases. This review evaluated the effects of LPV/RTV alone or in combination with standard care ± interferons/antiviral treatments compared to other therapies, regarding duration of hospital stay, risk of progressing to invasive mechanical, time to virological cure and body temperature normalization, cough relief, radiological progression, mortality and safety. (Results) A consensus was reached to select 32 articles for full-text screening; only 14 articles comprising 9036 patients were included in this study; and eight of these were included for meta-analysis. Most of these studies did not report positive clinical outcomes with LPV/RTV treatment. In terms of virological cure, three studies reported less time in days to achieve a virological cure for LPV/RTV arm relative to no antiviral treatment (−0.81 day; 95% confidence interval (CI), −4.44 to 2.81; p = 0.007, I2 = 80%). However, the overall effect was not significant (p = 0.66). When comparing the LPV/RTV arm to umifenovir arm, a favorable affect was observed for umifenovir arm, but not statically significant (p = 0.09). In terms of time to body normalization and cough relief, no favorable effects of LPV/RTV versus umifenovir were observed. The largest trials (RECOVERY and SOLIDARITY) have shown that LPV/RTV failed to reduce mortality, initiation of invasive mechanical ventilation or hospitalization duration. Adverse events were reported most frequently for LPV/RTV (n = 84) relative to other antivirals and no antiviral treatments. (Conclusions) This review did not reveal any significant advantage in efficacy of LPV/RTV for the treatment of COVID-19 over standard care, no antivirals or other antiviral treatments. This result might not reflect the actual evidence.
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46

Morán-Santibañez, Karla, Mario Peña-Hernández, Lucia Cruz-Suárez, Denis Ricque-Marie, Rachid Skouta, Abimael Vasquez, Cristina Rodríguez-Padilla, and Laura Trejo-Avila. "Virucidal and Synergistic Activity of Polyphenol-Rich Extracts of Seaweeds against Measles Virus." Viruses 10, no. 9 (August 30, 2018): 465. http://dx.doi.org/10.3390/v10090465.

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Although preventable by vaccination, Measles still causes thousands of deaths among young children worldwide. The discovery of new antivirals is a good approach to control new outbreaks that cause such death. In this study, we tested the antiviral activity against Measles virus (MeV) of Polyphenol-rich extracts (PPs) coming from five seaweeds collected and cultivated in Mexico. An MTT assay was performed to determine cytotoxicity effect, and antiviral activity was measured by syncytia reduction assay and confirmed by qPCR. PPs from Ecklonia arborea (formerly Eisenia arborea, Phaeophyceae) and Solieria filiformis (Rhodophyta) showed the highest Selectivity Index (SI), >3750 and >576.9 respectively. Both PPs extracts were selected to the subsequent experiments owing to their high efficacy and low cytotoxicity compared with ribavirin (SI of 11.57). The combinational effect of PPs with sulphated polysaccharides (SPs) and ribavirin were calculated by using Compusyn software. Synergistic activity was observed by combining both PPs with low concentrations of Solieria filiformis SPs (0.01 µg/mL). The antiviral activity of the best combinations was confirmed by qPCR. Virucidal assay, time of addition, and viral penetration evaluations suggested that PPs act mainly by inactivating the viral particle. To our knowledge, this is the first report of the virucidal effect of Polyphenol-rich extracts of seaweeds.
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47

Rona, Gergely, Andras Zeke, Bearach Miwatani-Minter, Maren de Vries, Ramanjit Kaur, Austin Schinlever, Sheena Faye Garcia, et al. "The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target." Cell Death & Differentiation 29, no. 2 (December 3, 2021): 285–92. http://dx.doi.org/10.1038/s41418-021-00900-1.

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AbstractThe risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a novel assay and in silico modeling and screening, we identified NSP14-NSP10 inhibitors that increase remdesivir’s potency. A model compound, sofalcone, both inhibits the exonuclease activity of SARS-CoV-2, SARS-CoV, and MERS-CoV in vitro, and synergistically enhances the antiviral effect of remdesivir, suppressing the replication of SARS-CoV-2 and the related human coronavirus OC43. The validation of top hits from our primary screenings using cellular systems provides proof-of-concept for the NSP14 complex as a therapeutic target.
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48

Franco, Evelyn J., Jaime L. Rodriquez, Justin J. Pomeroy, Kaley C. Hanrahan, and Ashley N. Brown. "The effectiveness of antiviral agents with broad-spectrum activity against chikungunya virus varies between host cell lines." Antiviral Chemistry and Chemotherapy 26 (January 2018): 204020661880758. http://dx.doi.org/10.1177/2040206618807580.

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Chikungunya virus (CHIKV) is a mosquito-borne virus that has recently emerged in the Western Hemisphere. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. This study aims to evaluate the antiviral activity of commercially available broad-spectrum antivirals against CHIKV. Due to host cell-specific variability in uptake and intracellular processing of drug, we evaluated the antiviral effects of each agent in three cell lines. Antiviral activities of ribavirin (RBV), interferon-alfa (IFN-α) and favipiravir (FAV) were assessed in CHIKV-infected Vero, HUH-7, and A549 cells. CHIKV-infected cells were treated with increasing concentrations of each agent for three days and viral burden was quantified by plaque assay on Vero cells. Cytotoxic effects of RBV, FAV and IFN-α were also evaluated. Antiviral activity differed depending on the cell line used for evaluation. RBV had the greatest antiviral effect in HUH-7 cells (EC50 = 2.575 µg/mL); IFN-α was most effective in A549 cells (EC50 = 4.235 IU/mL); and FAV in HUH-7 cells (EC50 = 20.00 μg/mL). The results of our study show FAV and IFN-α are the most promising candidates, as their use led to substantial reductions in viral burden at clinically achievable concentrations in two human-derived cell lines. FAV is an especially attractive candidate for further investigation due to its oral bioavailability. These findings also highlight the importance of cell line selection for preclinical drug trials.
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49

Bello-Morales, Raquel, Sabina Andreu, Vicente Ruiz-Carpio, Inés Ripa, and José Antonio López-Guerrero. "Extracellular Polymeric Substances: Still Promising Antivirals." Viruses 14, no. 6 (June 19, 2022): 1337. http://dx.doi.org/10.3390/v14061337.

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Sulfated polysaccharides and other polyanions have been promising candidates in antiviral research for decades. These substances gained attention as antivirals when they demonstrated a high inhibitory effect in vitro against human immunodeficiency virus (HIV) and other enveloped viruses. However, that initial interest was followed by wide skepticism when in vivo assays refuted the initial results. In this paper we review the use of sulfated polysaccharides, and other polyanions, in antiviral therapy, focusing on extracellular polymeric substances (EPSs). We maintain that, in spite of those early difficulties, the use of polyanions and, specifically, the use of EPSs, in antiviral therapy should be reconsidered. We base our claim in several points. First, early studies showed that the main disadvantage of sulfated polysaccharides and polyanions is their low bioavailability, but this difficulty can be overcome by the use of adequate administration strategies, such as nebulization of aerosols to gain access to respiratory airways. Second, several sulfated polysaccharides and EPSs have demonstrated to be non-toxic in animals. Finally, these macromolecules are non-specific and therefore they might be used against different variants or even different viruses.
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50

Tsang, Jessica Oi-Ling, Jie Zhou, Xiaoyu Zhao, Cun Li, Zijiao Zou, Feifei Yin, Shuofeng Yuan, Man-Lung Yeung, Hin Chu, and Jasper Fuk-Woo Chan. "Development of Three-Dimensional Human Intestinal Organoids as a Physiologically Relevant Model for Characterizing the Viral Replication Kinetics and Antiviral Susceptibility of Enteroviruses." Biomedicines 9, no. 1 (January 18, 2021): 88. http://dx.doi.org/10.3390/biomedicines9010088.

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Enteroviruses are important causes of hand, foot, and mouth disease, respiratory infections, and neurological infections in human. A major hurdle for the development of anti-enterovirus agents is the lack of physiologically relevant evaluation platforms that closely correlate with the in vivo state. We established the human small intestinal organoids as a novel platform for characterizing the viral replication kinetics and evaluating candidate antivirals for enteroviruses. The organoids supported productive replication of enterovirus (EV)-A71, coxsackievirus B2, and poliovirus type 3, as evidenced by increasing viral loads, infectious virus titers, and the presence of cytopathic effects. In contrast, EV-D68, which mainly causes respiratory tract infection in humans, did not replicate significantly in the organoids. The differential expression profiles of the receptors for these enteroviruses correlated with their replication kinetics. Using itraconazole as control, we showed that the results of various antiviral assays, including viral load reduction, plaque reduction, and cytopathic effect inhibition assays, were highly reproducible in the organoids. Moreover, itraconazole attenuated virus-induced inflammatory response in the organoids, which helped to explain its antiviral effects and mechanism. Collectively, these data showed that the human small intestinal organoids may serve as a robust platform for investigating the pathogenesis and evaluating antivirals for enteroviruses.
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