Favipiravir and Ribavirin Inhibit Replication of Asian and African Strains of Zika Virus in Different Cell Models

Abstract

Zika virus (ZIKV) has recently emerged as a new public health threat. ZIKV infections have caused a wide spectrum of neurological diseases, such as Guillain–Barré syndrome, myelitis, meningoencephalitis, and congenital microcephaly. No effective therapies currently exist for treating patients infected with ZIKV. Herein, we evaluated the anti-viral activity of favipiravir (T-705) and ribavirin against Asian and African strains of ZIKV using different cell models, including human neuronal progenitor cells (hNPCs), human dermal fibroblasts (HDFs), human lung adenocarcinoma cells (A549) and Vero cells. Cells were treated with favipiravir or ribavirin and effects on ZIKV replication were determined using quantitative real-time PCR and plaque assay. Our results demonstrate that favipiravir or ribavirin treatment significantly inhibited ZIKV replication in a dose-dependent manner. Moreover, favipiravir treatment of ZIKV-infected hNPCs led to reduced cell death, enhanced AKT pathway phosphorylation, and increased expression of anti-apoptotic factor B cell lymphoma 2. In conclusion, our results demonstrate conclusively that favipiravir inhibits ZIKV replication and prevents cell death, and can be a promising intervention for ZIKV-associated disease.

Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs

“…While some studies demonstrate that ZIKV replication remains unaffected by these drugs in stem cell-derived neurons, other investigations have proven their inhibitory activity during the treatment of neural progenitor cell lines (59, 60). The different efficacies of these molecules could be linked to possible divergences in the cellular uptake or metabolism of nucleoside drugs in these cell lines.…”

The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells

“…Huh7 cells (human liver cell line) were grown in DMEM (Gibco) supplemented with 5% heat-inactivated fetal bovine serum. Cells were infected with SARS-COV-2 or PBS (Mock) at a multiplicity of infection (MOI) of 1 for 2 hours (17,18,21,22). Cell were washed twice with PBS and media containing different concentrations of auranofin (Sigma) or DMSO (Sigma) was added to cells.…”

“…Forward (5′-GACCCCAAAATC AGCGAAAT-3′), reverse (5′-TCTGGTTACTGCCAGTTGAATCTG-3′), probe, (5′-FAM-ACCCCGCATTACGTTTGGTGGACC-BHQ1-3') targeting the SARS-COV-2 N1 gene and Forward (5′-TTACAAACATTGGCCGCAAA-3′), reverse (5′-GCGCGACATTCCGAAGAA3′), probe, (5′-FAM-ACAATTTGCCCCCAGCGCTTCAG-BHQ1-3') targeting the SARS-COV-2 N2 gene (Integrated DNA Technologies). Viral RNA copies were determined after comparison with a standard curve produced using serial 10-fold dilutions of SARS-COV-2 RNA (18,20).…”

“…We investigated the anti-viral activity of auranofin against SARS-CoV-2 and its effect on virus-induced inflammation in human cells. We infected Huh7 cells with SARS-CoV-2 (USA-WA1/2020) at a multiplicity of infection (MOI) of 1 for 2 hours, followed by the addition of 4 µM of auranofin (17,18). DMSO (0.1%) was used as control (the solvent was used to prepare drug stock).…”

Antivirals in medical biodefense

“…The use and potential benefits of multidrug cocktails, mainly reduction of resistance mutation and toxicity through dose reduction, have been pointed out by many authors, including in the context of yellow fever treatment [103]. Examples for synergistic effects in combinations of antiviral compounds with similar or different MoA are ribavirin with vitamin A in measles infections [12], ribavirin with favipiravir in Zika virus infections [75], and ribavirin with mefenamic acid in infections with Chikungunya virus [126]. Antiviral drug combinations may also be a way to deal with emerging antiviral drug resistance [74].…”