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

Kumar, Prateek; Bhardwaj, Taniya; Kumar, Ankur; Gehi, Bhuvaneshwari R.; Kapuganti, Shivani K.; Garg, Neha; Nath, Gopal; Giri, Rajanish

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