Reprofiling of approved drugs against SARS-CoV-2 main protease: an in-silico study

Given the COVID-19 pandemic, currently, there are many drugs in clinical trials against this virus. Among the excellent drug targets of SARS-CoV-2 are its proteases (Nsp3 and Nsp5) that plays vital role in polyprotein processing giving rise to functional nonstructural proteins, essential for viral replication and survival. Nsp5 (also known as M-pro) hydrolyzes replicase polyprotein (1ab) at eleven different sites. For targeting M-pro, we have employed drug repurposing approach to identify potential inhibitors of SARS-CoV-2 in a shorter time span. Screening of approved drugs through docking reveals Hyaluronic acid and Acarbose among the top hits which are showing strong interactions with catalytic site residues of M-pro. We have also performed docking of drugs Lopinavir, Ribavirin, and Azithromycin on SARS-CoV-2 M-pro. Further, binding of these compounds (Hyaluronic acid, Acarbose, and Lopinavir) is validated by extensive molecular dynamics simulation of 500 ns where these drugs show stable binding with M-pro. We believe that the high-affinity binding of these compounds will help in designing novel strategies for structure-based drug discovery against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

Automated summary

This study investigates drug repurposing for the proteases of SARS-CoV-2, identifying potential inhibitors such as hyaluronic acid and acarbose. Molecular dynamics simulation confirms the stable binding of these drugs with the proteases, suggesting their potential for structure-based drug discovery against SARS-CoV-2.