Abstract
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.
Keywords: COVID-19; Mpro; Nsp5; SARS-CoV-2; approved drug; protease.
【저자키워드】 COVID-19, SARS-CoV-2, protease, MPro, nsp5, approved drug, 【초록키워드】 clinical trial, Drug discovery, Azithromycin, COVID-19 pandemic, Lopinavir, drug, docking, protease, virus, Screening, Molecular dynamics simulation, Hyaluronic acid, nonstructural proteins, survival, viral replication, drug target, binding, Interaction, inhibitors of SARS-CoV-2, residue, M pro, help, catalytic site, polyprotein, high-affinity binding, approach, acarbose, identify, performed, approved, functional, these compound, reveal, 【제목키워드】 in-silico,