Evaluation of sofosbuvir activity and resistance profile against West Nile virus in vitro.

In this study, the in vitro antiviral activity of sofosbuvir against West Nile virus (WNV) was determined by plaque assay (PA) and Immunodetection Assay (IA) in human cell lines and by enzymatic RdRp assay. By PA, the sofosbuvir half-maximal inhibitory concentration (IC50) was 1.2 ± 0.3 μM in Huh-7, 5.3 ± 0.9 μM in U87, 7.8 ± 2.5 μM in LN-18 and 63.4 ± 14.1 μM in A549 cells. By IA, anti-WNV activity was confirmed in both hepatic (Huh-7, 1.7 ± 0.5 μM) and neuronal (U87, 7.3 ± 2.0 μM) cell types. Sofosbuvir was confirmed to inhibit the purified WNV RdRp (IC50 11.1 ± 4.6 μM). In vitro resistance selection experiments were performed by propagating WNV in the Huh-7 cell line with two-fold increasing concentrations of sofosbuvir. At 80 μM, a significantly longer time for viral breakthrough was observed compared with lower concentrations (18 vs. 7-9 days post infection; p = 0.029), along with the detection of the S604T mutation, corresponding to the well-known S282T substitution in the motif B of HCV NS5B, which confers resistance to sofosbuvir. Molecular docking experiments confirmed that the S604T mutation within the catalytic site of RdRp affected the binding mode of sofosbuvir. To our knowledge, this is the first report of the antiviral activity of sofosbuvir against WNV as well as of selection of mutants in vitro. PMID: 31931104 [PubMed - as supplied...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research

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In this study, the in vitro antiviral activity of sofosbuvir against West Nile virus (WNV) was determined by plaque assay (PA) and Immunodetection Assay (IA) in human cell lines and by enzymatic RdRp assay. By PA, the sofosbuvir half-maximal inhibitory concentration (IC50) was 1.2 ± 0.3 μM in Huh-7, 5.3 ± 0.9 μM in U87, 7.8 ± 2.5 μM in LN-18 and 63.4 ± 14.1 μM in A549 cells. By IA, anti-WNV activity was confirmed in both hepatic (Huh-7, 1.7 ± 0.5 μM) and neuronal (U87, 7.3 ± 2.0 μM) cell types. Sofosbuvir was confirmed to inhi...
Source: Antiviral Therapy - Category: Virology Source Type: research
Contributors : Nandan S Gokhale ; Alexa B McIntyre ; Melissa D Mattocks ; Christopher L Holley ; Helen M Lazear ; Christopher E Mason ; Stacy M HornerSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThe RNA modification N6-methyladenosine (m6A) can modulate mRNA fate and thus affect many biological processes. We analyzed m6A modification across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m6A modification of specific cellular...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : Alexa B McIntyre ; Nandan S Gokhale ; Helen M Lazear ; Christopher L Holley ; Christopher E Mason ; Stacy M HornerSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensThe modification N6-methyladenosine (m6A) affects rates of translation and degradation of mRNA transcripts. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV) using MeRIP-seq. We used the uninfected replicates, among which we would expect little biological variation in methylation, as negative control...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Other Homo sapiens Source Type: research
María Maximina B. Moreno-Altamirano1*, Simon E. Kolstoe2 and Francisco Javier Sánchez-García1* 1Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico 2School of Health Sciences, University of Portsmouth, Portsmouth, United Kingdom Over the last decade, there has been significant advances in the understanding of the cross-talk between metabolism and immune responses. It is now evident that immune cell effector function strongly depends on the metabolic pathway in w...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ZIKV replication in vitro showed median inhibitory concentrations (IC50) of 13.87 ± 1.09 μM and 33.33 ± 1.13 μM in Vero and A549 cells, respectively; without showing any cytotoxic effect in both cell lines (median cytotoxic concentration (CC50)> 1,000 μM). Moreover, ATA protected both cell types from ZIKV-induced cytopathic effect (CPE) and apoptosis in a time- and concentration-dependent manner. In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
n-Acebes MA Abstract Flaviviruses are positive strand RNA viruses distributed all over the world that infect millions of people every year, and for which no specific antiviral agents have been approved. These viruses include the mosquito-borne West Nile virus (WNV) responsible for outbreaks of meningitis and encephalitis. Considering that nordihydroguaiaretic acid (NDGA) has been previously shown to inhibit the multiplication of the related dengue virus and hepatitis C virus, we have evaluated the effect of NDGA, and its methylated derivative tetra-O-methyl nordihydroguaiaretic (M4N), on the infection of WNV. Both...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Conclusions:It is important to suspect HAV infection when the patient with encephalitis or myelitis have abnormal liver function.Disclosure: Dr. Jo has nothing to disclose. Dr. Baek has nothing to disclose. Dr. Jeon has nothing to disclose. Dr. Lee has nothing to disclose.
Source: Neurology - Category: Neurology Authors: Tags: Zika, Chikungunya, West Nile Virus, and Other Viral Infections II Source Type: research
Abstract Over 110 million units of blood are collected yearly. The need for blood products is greater in developing countries, but so is the risk of contracting a transfusion-transmitted infection. Without efficient donor screening/viral testing and validated pathogen inactivation technology, the risk of transfusion-transmitted infections correlates with the infection rate of the donor population. The World Health Organization has published guidelines on good manufacturing practices in an effort to ensure a strong global standard of transfusion and blood product safety. Sub-Saharan Africa is a high-risk region for...
Source: Blood Transfusion - Category: Hematology Authors: Tags: Blood Transfus Source Type: research
Abstract Protein-protein interactions govern biological functions in cells, in the extracellular milieu and at the border between cells and extracellular space. Viruses are small intracellular parasites and thus rely on protein interactions to produce progeny inside host cells and to spread from cell to cell. Usage of host proteins by viruses can have severe consequences e.g. apoptosis, metabolic disequilibria or altered cell proliferation and mobility. Understanding protein interactions during virus infection can thus educate us on viral infection and pathogenesis mechanisms. Moreover, it has led to important cli...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research
We report here on an approach targeting the host reactive cysteinome to identify inhibitors of host factors required for the infectious cycle of Flaviviruses and other viruses. We used cellular phenotypic screens to identify a series of covalent inhibitors, exemplified by QL-XII-47, that are active against dengue virus. We demonstrate that the compounds effectively block viral protein expression. This inhibition is associated with repression of downstream processes of the infectious cycle, and thus significantly contributes to the potent antiviral activity of these compounds. We demonstrate that QL-XII-47's antiviral activ...
Source: Antiviral Therapy - Category: Virology Source Type: research
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