Multiple studies are carried out to explore the benefits of antiviral drugs, especially hepatitis C virus direct-acting antivirals (HCV DAAs) to treat COVID-19. This study was conducted to evaluate the anti-SARS-CoV-2 effects of asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor) and sofosbuvir (an RNA polymerase inhibitor). Vero E6, Calu-3, Huh7.5, and HEK293T cell lines were used for testing the antiviral activity of the drugs against SARS-CoV-2 in vitro.
Asunaprevir inhibited the SARS-CoV-2- induced cytopathic effects in Vero E6 cells and blocked SARS-CoV-2 infection in Vero E6 cells with an IC50 value of 4.669 μM as compared to Remdisevir (IC50 = 0.098 μM) used as a positive control. Moreover, asunaprevir inhibited HCV propagation in Huh7.5 infected cells with an IC50 value of 0.279 μM. Furthermore, asunaprevir also decreased the TMPRSS2-mediated luciferase activity which is involved in the early infection stage of the SARS-CoV-2 life cycle. Additionally, asunaprevir also suppressed the SARS-CoV-2 propagation in human lung cells (Calu-3).
Overall, the results indicate that asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by the treatment with asunaprevir. Though asunaprevir has a broad spectrum of antiviral activity against RNA viruses, further studies are required to demonstrate the mode of action by which asunaprevir affects the entry of SARS-CoV-2. Asunaprevir may be a promising candidate for drug repurposing against COVID-19. However, thorough clinical trials are needed to confirm the safety and efficacy of asunaprevir in COVID-19 patients.
Source: Molecular Cells
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