Antiviral drugs prioritization for COVID-19 management based on rational selection

Abstract

The SARS-CoV-2 infection has resulted in COVID-19 pandemic worldwide. It has infected around 0.1 bil-lion individuals and caused 2 million fatalities across the globe till mid-January 2021. Drug repurposing has been utilized as the most preferred therapeutic intervention for COVID-19 mitigation due to its necessity and feasibility. To prioritize therapeutic regime against COVID-19, we used 61 antiviral drugs and their combinations. Selected molecules were sub-jected to virtual screening against: (i) human angio-tensin-converting enzyme 2 receptor binding domain (hACE-2) which serves as an anchor for virus attach-ment and entry, (ii) SARS-CoV-2 RNA dependent RNA polymerase (RdRp) responsible for viral RNA replication, and (iii) SARS-CoV-2 main protease (MPro) needed for viral polyprotein slab proteolytic processing. Based on docking score, pharmacodyna-mic and pharmacokinetic parameters, combinations of Daclatasvir, Elbasvir, Indinavir, Ledipasvir, Paritaprevir and Rilpivirine were analysed further. Our analysis suggested Sofosbuvir in combination with Ledipasvir and Daclatasvir as potential thera-peutic agents for SARS-CoV-2. The combined score suggests that these combinations have superior anti-SARS-CoV-2 potential than Remdesivir and other in-vestigational drugs. The present work provides a ra-tionale-based approach to select drugs with possible anti-SARS-CoV-2 activity for further clinical evalua-tion.