Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy

• Published in: Bioscience reports Vol. 40; no. 6
• Main Authors: Shamsi, Anas, Mohammad, Taj, Anwar, Saleha, AlAjmi, Mohamed F, Hussain, Afzal, Rehman, Md Tabish, Islam, Asimul, Hassan, Md Imtaiyaz
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd 26-06-2020
• Subjects: Antiviral Agents - chemistry; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Betacoronavirus - drug effects; Betacoronavirus - enzymology; Bioinformatics; Computational Biology; Computer Simulation; Drug Evaluation, Preclinical - methods; Maraviroc - chemistry; Maraviroc - metabolism; Maraviroc - pharmacology; Molecular Structure; Protease Inhibitors - chemistry; Protease Inhibitors - metabolism; Protease Inhibitors - pharmacology; Quinoxalines - chemistry; Quinoxalines - metabolism; Quinoxalines - pharmacology; SARS-CoV-2; Structural Biology; Sulfonamides - chemistry; Sulfonamides - metabolism; Sulfonamides - pharmacology; Virology; SARS-CoV-2; drug repurposing; molecular docking; Coronavirus disease 2019; virtual screening; FDA approved drugs
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20201256

Due to the lack of efficient therapeutic options and clinical trial limitations, the FDA-approved drugs can be a good choice to handle Coronavirus disease (COVID-19). Many reports have enough evidence for the use of FDA-approved drugs which have inhibitory potential against target proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we utilized a structure-based drug design approach to find possible drug candidates from the existing pool of FDA-approved drugs and checked their effectiveness against the SARS-CoV-2. We performed virtual screening of the FDA-approved drugs against the main protease (Mpro) of SARS-CoV-2, an essential enzyme, and a potential drug target. Using well-defined computational methods, we identified Glecaprevir and Maraviroc (MVC) as the best inhibitors of SARS-CoV-2 Mpro. Both drugs bind to the substrate-binding pocket of SARS-CoV-2 Mpro and form a significant number of non-covalent interactions. Glecaprevir and MVC bind to the conserved residues of substrate-binding pocket of SARS-CoV-2 Mpro. This work provides sufficient evidence for the use of Glecaprevir and MVC for the therapeutic management of COVID-19 after experimental validation and clinical manifestations.