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Articles de revues sur le sujet "VIRAL-LIKE TOXICITY"
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Liu, Di, Jingjing Tian, Guangxing Liu et Huancai Yin. « Development of Influenza H7N9 Virus Like Particle and Its Application in the Delivery of Fluorescent Quantum Dots ». Nanoscience and Nanotechnology Letters 11, no 12 (1 décembre 2019) : 1750–55. http://dx.doi.org/10.1166/nnl.2019.3066.
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Quantum dots are widely used in biomedical investigation, but the application is often limited by their systemic toxicity. This paper aimed to investigate the effects of virus like particles coating on the toxicity and cellular accumulation of quantum dots, providing a new paradigm for the design of intracellular microscopic probes. For this purpose, an H7N9 virus like particle composed of unmodified hemagglutinin, neuraminidase and the matrix 1 protein from the A/Shanghai/02/2013 strain were produced in Spodoptera frugiperda insect cells. After then, quantum dots successfully self-assembled into viral like particles with an incorporation efficiency of about 80%, exhibiting enhanced accumulation and minimal toxicity in HepG2 cells. Together, the data demonstrated that recombinant H7N9 virus like particle could be developed as a promising carrier for the delivery of nanoparticles and other relating drugs. And future work would be carried out on the development of incorporation efficiency of quantum dots.
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Rehman, Mubashar. « Nano-Technological Approach towards Anti-Viral Therapy ». Global Immunological & ; Infectious Diseases Review I, no I (30 décembre 2016) : 12–20. http://dx.doi.org/10.31703/giidr.2016(i-i).02.
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With time viral infections are increasing day by day due to various reasons like new viruses, the resistance of viruses to antiviral therapy, and mutation of one form of the virus to another form; these types of problems create many challenges in the field of research. Furthermore, a lot of challenges are encountered in the treatment of antiviral therapy, like interaction with other medication and use of increased frequency and a high dose of antiviral due to infection in CNS or synovial fluid where drug permeation is less. Consequently, toxicity and other side effect chances will be more. Nano-technological approaches are used to overcome these challenges. The beneficial properties come from such engineering, including stimuli sensitivity, targetability, and longevity; these are all combined to give multifunctional nano-carriers that concurrently execute different beneficial tasks
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Hamid, Oday, Mary L. Varterasian, Scott Wadler, J. Randolph Hecht, Al Benson, Evanthia Galanis, Margaret Uprichard et al. « Phase II Trial of Intravenous CI-1042 in Patients With Metastatic Colorectal Cancer ». Journal of Clinical Oncology 21, no 8 (15 avril 2003) : 1498–504. http://dx.doi.org/10.1200/jco.2003.09.114.
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Purpose: To evaluate the antitumor activity, safety, immune response, and replication of CI-1042 (ONYX-015), an E1B 55-kd gene-deleted replication-selective adenovirus, administered intravenously to patients with metastatic colorectal cancer Patients and Methods: Eighteen patients with metastatic colorectal cancer for whom prior chemotherapy failed were enrolled onto an open-label, multicenter, phase II study. CI-1042 was administered intravenously at a dose of 2 × 1012 viral particles every 2 weeks. Patients were evaluated for tumor response and toxicity; in addition, blood samples were taken for adenovirus DNA and neutralizing antibody analysis. Results: Common toxicities included flu-like symptoms, nausea, and emesis. All 18 patients eventually were removed from study because of progressive disease. Seven patients were assessed as having stable disease after 2 months of treatment, whereas two patients were considered to have stable disease after 4 months. Detectable circulating CI-1042 DNA was identified in 36% of patients 72 hours after last infusion, which is suggestive of ongoing viral replication. Conclusion: In this phase II study, intravenous CI-1042 was administered safely to patients with advanced colorectal cancer. Toxicity was manageable, consisting primarily of flu-like symptoms. Stable disease was experienced by seven patients for 11 to 18 weeks.
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Sohrab, Sayed Sartaj, Sherif Aly El-Kafrawy, Zeenat Mirza, Mohammad Amjad Kamal et Esam Ibraheem Azhar. « Design and Delivery of Therapeutic siRNAs : Application to MERS-Coronavirus ». Current Pharmaceutical Design 24, no 1 (22 mars 2018) : 62–77. http://dx.doi.org/10.2174/1381612823666171109112307.
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Background: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April 2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published. Methods: In this review, we have discussed the computational designing and delivery of potential siRNAs. Potential siRNA can be designed to silence a desired gene by considering many factors like target site, specificity, length and nucleotide content of siRNA, removal of potential off-target sites, toxicity and immunogenic responses. The efficient delivery of siRNAs into targeted cells faces many challenges like enzymatic degradation and quick clearance through renal system. The siRNA can be delivered using transfection, electroporation and viral gene transfer. Currently, siRNAs delivery has been improved by using advanced nanotechnology like lipid nanoparticles, inorganic nanoparticles and polymeric nanoparticles. Conclusion: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative technology has attracted researchers, academia and pharmaceuticals industries towards designing and development of highly effective and targeted disease therapy. By using this technology, effective and potential siRNAs can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against MERS-CoV.
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Fang, Shangling, Li Wang, Wei Guo, Xia Zhang, Donghai Peng, Chunping Luo, Ziniu Yu et Ming Sun. « Bacillus thuringiensis Bel Protein Enhances the Toxicity of Cry1Ac Protein to Helicoverpa armigera Larvae by Degrading Insect Intestinal Mucin ». Applied and Environmental Microbiology 75, no 16 (19 juin 2009) : 5237–43. http://dx.doi.org/10.1128/aem.00532-09.
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ABSTRACT Bacillus thuringiensis has been used as a bioinsecticide to control agricultural insects. Bacillus cereus group genomes were found to have a Bacillus enhancin-like (bel) gene, encoding a peptide with 20 to 30% identity to viral enhancin protein, which can enhance viral infection by degradation of the peritrophic matrix (PM) of the insect midgut. In this study, the bel gene was found to have an activity similar to that of the viral enhancin gene. A bel knockout mutant was constructed by using a plasmid-free B. thuringiensis derivative, BMB171. The 50% lethal concentrations of this mutant plus the cry1Ac insecticidal protein gene were about 5.8-fold higher than those of the BMB171 strain. When purified Bel was mixed with the Cry1Ac protein and fed to Helicoverpa armigera larvae, 3 μg/ml Cry1Ac alone induced 34.2% mortality. Meanwhile, the mortality rate rose to 74.4% when the same amount of Cry1Ac was mixed with 0.8 μg/ml of Bel. Microscopic observation showed a significant disruption detected on the midgut PM of H. armigera larvae after they were fed Bel. In vitro degradation assays showed that Bel digested the intestinal mucin (IIM) of Trichoplusia ni and H. armigera larvae to various degrading products, similar to findings for viral enhancin. These results imply Bel toxicity enhancement depends on the destruction of midgut PM and IIM, similar to the case with viral enhancin. This discovery showed that Bel has the potential to enhance insecticidal activity of B. thuringiensis-based biopesticides and transgenic crops.
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León-Gutiérrez, Gabriela, Carlos Cabello-Gutiérrez, Mario Héctor Martínez-Gómez, Pedro Azuara, Brian Madden, Jaime Shalkow et Armando Mejía. « Secondary Metabolites in Functionalized Titanium Dioxide (TIO<sub>2</sub>) Nanoparticles : A Novel and Safe Virucide against SARS-CoV-2 ». Journal of Nano Research 70 (25 octobre 2021) : 137–45. http://dx.doi.org/10.4028/www.scientific.net/jnanor.70.137.
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Nanotechnology and nanomedicine have been shown to provide a novel and safe platform to combat a variety of viruses like SARS-CoV-2. Secondary metabolites implanted into a carrier of functionalized titanium dioxide (TiO2) nanoparticles (SMNP) were tested for efficacy versus SARS-CoV-2 infectivity, and cytotoxicity on healthy cells. Viral load; from a clinical point of view, it is not as important as the number of infective viral particles, which relates to the viral particles capable of causing the disease. To measure viral infectivity SARS-CoV-2 was placed into cell cultures and evaluating the destructive effect on cultured cells. In this system, SMNP demonstrated significant reduction of viral infectivity in vitro. Lytic plaques of viral infectivity were observed at a dilution of 4x10-8 in VERO E6 cells, while SARS-CoV-2 preincubated with the SMNP compound, tissue damage was observed only up to the 3x10-5 dilution. SMNP reduced the number of infective viral particles by 3 orders of magnitude. Surprising minimal toxicity to healthy cells was observed when compared to other commercially available antiseptics (glutaraldehyde, chlorine, chlorhexidine, ethanol and Lysol™), cell viability decreased only by 5.5%. SMNP is a safe and effective antiviral against SARS-CoV-2, and further studies are warranted to explore this compound further.
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Ennishi, Daisuke, Yoshinobu Maeda, Nozomi Niitsu, Minoru Kojima, Koji Izutsu, Jun Takizawa, Shigeru Kusumoto et al. « Hepatic toxicity and prognosis in hepatitis C virus–infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens : a Japanese multicenter analysis ». Blood 116, no 24 (9 décembre 2010) : 5119–25. http://dx.doi.org/10.1182/blood-2010-06-289231.
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Abstract The influence of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)–like chemotherapy. Survival outcomes and hepatic toxicity were compared according to HCV infection. The median follow-up was 31 and 32 months for patients who were HCV-positive and HCV-negative, respectively. HCV infection was not a significant risk factor for prognosis (3-year progression-free survival, 69% vs 77%, P = .22; overall survival, 75% vs 84%, P = .07). Of 131 patients who were HCV-positive, 36 (27%) had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients who were HCV-negative. Multivariate analysis revealed that HCV infection was a significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95% confidence interval, 6.37-34.03; P < .001). An exploratory analysis revealed that pretreatment transaminase was predictive of severe hepatic toxicity. HCV-RNA levels significantly increased during immunochemotherapy (P = .006). These results suggest that careful monitoring of hepatic function and viral load is indicated during immunochemotherapy for HCV-positive patients.
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Goldenberg, Seth J., Jeffrey L. McDermott, Tauseef R. Butt, Michael R. Mattern et Benjamin Nicholson. « Strategies for the identification of novel inhibitors of deubiquitinating enzymes ». Biochemical Society Transactions 36, no 5 (19 septembre 2008) : 828–32. http://dx.doi.org/10.1042/bst0360828.
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Dysregulation of the UPS (ubiquitin–proteasome system) has been implicated in a wide range of pathologies including cancer, neurodegeneration and viral infection. Inhibiting the proteasome has been shown to be an effective therapeutic strategy in humans; yet toxicity with this target remains high. DUBs (deubiquitinating enzymes) represent an alternative target in the UPS with low predicted toxicity. Currently, there are no DUB inhibitors that have been used clinically. To address this situation, Progenra has developed a novel assay to measure the proteolytic cleavage of Ub (ubiquitin) or UBL (Ub-like protein) conjugates such as SUMO (small Ub-related modifier), NEDD8 (neural-precursor-cell-expressed, developmentally down-regulated 8) or ISG15 (interferon-stimulated gene 15) by isopeptidases. In this review, current platforms for detecting DUB inhibitors are discussed and the advantages and disadvantages of the approaches are underlined.
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Obermann, Wiebke, Alexandra Friedrich, Ramakanth Madhugiri, Paul Klemm, Jan Philipp Mengel, Torsten Hain, Stephan Pleschka et al. « Rocaglates as Antivirals : Comparing the Effects on Viral Resistance, Anti-Coronaviral Activity, RNA-Clamping on eIF4A and Immune Cell Toxicity ». Viruses 14, no 3 (3 mars 2022) : 519. http://dx.doi.org/10.3390/v14030519.
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Rocaglates are potent broad-spectrum antiviral compounds with a promising safety profile. They inhibit viral protein synthesis for different RNA viruses by clamping the 5′-UTRs of mRNAs onto the surface of the RNA helicase eIF4A. Apart from the natural rocaglate silvestrol, synthetic rocaglates like zotatifin or CR-1-31-B have been developed. Here, we compared the effects of rocaglates on viral 5′-UTR-mediated reporter gene expression and binding to an eIF4A-polypurine complex. Furthermore, we analyzed the cytotoxicity of rocaglates on several human immune cells and compared their antiviral activities in coronavirus-infected cells. Finally, the potential for developing viral resistance was evaluated by passaging human coronavirus 229E (HCoV-229E) in the presence of increasing concentrations of rocaglates in MRC-5 cells. Importantly, no decrease in rocaglate-sensitivity was observed, suggesting that virus escape mutants are unlikely to emerge if the host factor eIF4A is targeted. In summary, all three rocaglates are promising antivirals with differences in cytotoxicity against human immune cells, RNA-clamping efficiency, and antiviral activity. In detail, zotatifin showed reduced RNA-clamping efficiency and antiviral activity compared to silvestrol and CR-1-31-B, but was less cytotoxic for immune cells. Our results underline the potential of rocaglates as broad-spectrum antivirals with no indications for the emergence of escape mutations in HCoV-229E.
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Firdayani, A. Riswoko et I. Helianti. « Inhibition of SARS-Cov-2 proteases by medicinal plant bioactive constituents : Molecular docking simulation ». IOP Conference Series : Earth and Environmental Science 976, no 1 (1 février 2022) : 012054. http://dx.doi.org/10.1088/1755-1315/976/1/012054.
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Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that has caused the corona pandemic since 2019 or known as Covid-19. The cleavage of its polyprotein started this viral replication into functional viral proteins by two proteases: 3-chymotrypsin-like protease (3CL protease), also known as main protease (Mpro), and Papain-like protease (PLpro). Medicinal plant bioactive constituents could potentially become protease inhibitor agents of this virus and prevent viral replication. Thus, further might be developed into drug candidates for diseases with no specific drug currently available. The first step of discovering the medicine is virtual screening with a molecular docking simulation approach. The stable conformation structure of the bioactive compounds was docked into the enzymes SARS-CoV-2 Main Protease (PDB ID: 6XMK) and SARS-CoV-2 Papain-Like Protease (PDB ID: 7CMD). Molecular docking simulations were operated using Molegro Virtual Docker (MVD) program after the validation process. In this study, analysis of the docking simulation was carried out of compounds in Andrographis paniculata, Phyllanthus niruri L., Aloe vera, and Sonchus arvensis. They are medicinal plants that have been used as a medicine for generations and may have potential as antivirals. A docking score with a more negative presentation binding energy value has a more significant potential to be a lead compound. Several potential compounds were evaluated for their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. This method can reduce the trial and error factor in the drug discovery stage, although it needs further proof by experimentation in a wet laboratory.
Livres sur le sujet "VIRAL-LIKE TOXICITY"
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Al-Darraji, Haider A., et Frederick L. Altice. The Perfect Storm. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199374847.003.0008.
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Globally, tuberculosis (TB) is a major cause of morbidity and mortality among people who use drugs (PWUD), particularly those co-infected with HIV. This chapter describes how TB is prevalent in several prison systems by virtue of the concentration of PWUD and people living with HIV. TB is further amplified within this system through overcrowding, poor ventilation, and delayed access to quality prevention and treatment services. In many countries, individuals cycling through prisons are inadequately screened and treated for TB, and affected individuals may have frequent treatment interruptions. For PWUD, relapse to drug use immediately after release from custody can impede continuity of care, which may contribute to the development of drug-resistant TB. Particularly in countries with high incarceration rates, prisons act as amplifiers of TB and drug-resistant TB in the community. The World Health Organization’s recommendations for integration of TB, HIV, and addiction treatment are seldom achieved, especially within prisons. Other factors contributing to poor TB outcomes among PWUD interfacing with prisons include insufficient support to promote medication adherence and co-morbidities, like viral hepatitis that potentiate hepatic toxicity, both of which are prevalent among PWUD.
Chapitres de livres sur le sujet "VIRAL-LIKE TOXICITY"
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William Tong, C. Y. « Antivirals ». Dans Tutorial Topics in Infection for the Combined Infection Training Programme. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198801740.003.0059.
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Viruses are obligate intracellular pathogens that utilize many of the host metabolic machineries for reproduction. Unlike the binary fission of bacteria, the replication process of viruses is more like a production line with a final assembly process to produce their progenies. Any agents used to prevent viral replication must be specific to the virus and cause as little problem for the host as possible. The rate of virus replication can also cause problems. In rapidly reproducing viruses, the high replication rate generates mutants that could be selected for resistance to antivirals. On the other hand, viruses could remain latent with little metabolic activity. None of the current antivirals are effective against latent viruses. The life cycle of a typical virus goes through the following stages: ● Attachment; ● Entry and uncoating; ● Replication of viral nucleic acid; ● Establishing latency or persistent infection (in some viruses); ● Translation of viral protein and post-translational modifications; ● Secretion and assembly of viral particles; and ● Release from host cells. Each of these steps can be used as antiviral targets. The most common strategy is to use a nucleoside analogue as a false substrate. However, such a false substrate can also be taken up by host polymerase and could result in toxicity, e.g. mitochondrial toxicity in some of the earlier antiretroviral drugs. The most successful example to circumvent this problem is aciclovir, which is the prodrug of the active agent aciclovir tri-phosphate. Aciclovir is a substrate for the viral enzyme thymidine kinase carried by the herpes simplex virus (HSV) and varicella-zoster virus (VZV), which converts it into aciclovir monophosphate. As this only happens inside cells infected by HSV or VZV, it is concentrated only in infected cells. Host enzymes then add further phosphates to form the active agent aciclovir triphosphate, which has a higher affinity to viral polymerase than host polymerase. It acts as a false substrate for the viral polymerase and results in premature termination of nucleic acid replication. A similar mechanism is utilized in ganciclovir against cytomegalovirus (CMV). The viral phosphate kinase involved in the case of CMV is the UL97 protein.
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Roychoudhury, Rajarshi. « Polymeric Nanomaterials for Cancer Theranostics ». Dans Bionanotechnology : Next-Generation Therapeutic Tools, 84–97. BENTHAM SCIENCE PUBLISHERS, 2022. http://dx.doi.org/10.2174/9789815051278122010006.
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Despite global efforts for decades, the number of cancer cases is still on the rise. Although in recent times there has been significant improvement in immunotherapy, chemotherapy remains standard care for cancer patients alongside radiation and surgery. Chemotherapeutic drugs and diagnostic agents (MRI, PET, Ultrasound) lack specificity and often suffer from poor solubility and unwanted biodistribution. This results in unnecessary high dose requirements, systemic toxicity, and compromised quality of life for the patients. Beside therapy, early diagnosis is essential for the successful treatment and cure of cancer patients, just like any other disease. Therefore, a suitable delivery vehicle is always needed for the theranostic agents. Viral vectors are routinely used for the delivery of genetic material. But parallelly, nanoparticles made with biodegradable, non-toxic, and non-immunogenic polymers are often used as a carrier of chemotherapy drugs, diagnostic agents as well as genetic materials. Once decorated with specific ligands, these nanocontainers can deliver cargo molecules to target tissue and organs with high precision.