Remdesivir and Ledipasvir among the FDA-Approved Antiviral Drugs Have Potential to Inhibit SARS-CoV-2 Replication

The rapid spread of the virus, the surge in the number of deaths, and the unavailability of specific SARS-CoV-2 drugs thus far necessitate the identification of drugs with anti-COVID-19 activity. SARS-CoV-2 enters the host cell and assembles a multisubunit RNA-dependent RNA polymerase (RdRp) complex of viral nonstructural proteins that plays a substantial role in the transcription and replication of the viral genome. Therefore, RdRp is among the most suitable targets in RNA viruses. Our aim was to investigate the FDA approved antiviral drugs having potential to inhibit the viral replication. The methodology adopted was virtual screening and docking of FDA-approved antiviral drugs into the RdRp protein. Top hits were selected and subjected to molecular dynamics simulations to understand the dynamics of RdRp in complex with these drugs. The antiviral activity of the drugs against SARS-CoV-2 was assessed in Vero E6 cells. Notably, both remdesivir (half-maximal effective concentration (EC50) 6.6 mu M, 50% cytotoxicity concentration (CC50) > 100 mu M, selectivity index (SI) = 15) and ledipasvir (EC50 34.6 mu M, CC50 > 100 mu M, SI > 2.9) exerted antiviral action. This study highlights the use of direct-acting antiviral drugs, alone or in combination, for better treatments of COVID-19.

Automated summary

This study investigated FDA-approved antiviral drugs for their potential to inhibit viral replication in COVID-19. The findings showed that both remdesivir and ledipasvir exerted antiviral action, highlighting the potential use of direct-acting antiviral drugs in the treatment of COVID-19.