| Autor: |
Kumar P; School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India., Bhardwaj T; School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India., Kumar A; School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India., Gehi BR; School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India., Kapuganti SK; School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India., Garg N; Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India., Nath G; Department of Microbiology, Faculty of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India., Giri R; School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India. |
| Abstrakt: |
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. |
