Abstract
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.
Highlights
Coronavirus disease (COVID-19) is a public health emergency across the globe that emerged from Wuhan, China in 2019
We analyzed the structures of SARS-CoV-2 main protease (Mpro) co-crystallized with different inhibitors and explored their binding pattern and mechanism of inhibition
Interaction analysis of the co-crystallized inhibitors binding to the substrate-binding site provides structural insights into the design of substrate-based inhibitors targeting SARS-CoV-2 Mpro
Summary
Coronavirus disease (COVID-19) is a public health emergency across the globe that emerged from Wuhan, China in 2019. The causative agent of COVID-19 is a newly modified form of SARS coronavirus (SARS-CoV) that has increased pathogenicity and spread, known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1]. Coronaviruses (COVs) are a group of extremely diverse, enveloped, positive-sense, and single-stranded RNA viruses [6], which cause a broad spectrum of respiratory, enteric, hepatic, and neurological diseases with varying severity among humans and animals [7]. Six COV species were known to cause human diseases [8]. Out of these six, four viruses namely: 229E, OC43, NL63, and HKU1 are prevalent and characteristically cause common cold symptoms in the immunocompetent individuals [8].
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