Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors. (October 2020)

• Record Type: Journal Article
• Authors: Jiménez-Alberto, Alicia; Ribas-Aparicio, Rosa María; Aparicio-Ozores, Gerardo; Castelán-Vega, Juan A.
• Is Part Of: Computational biology and chemistry. Volume 88(2020)
• Publication Date: 2020-10
• Subjects: Mpro -- SARS-CoV-2 -- COVID-19 -- Docking -- Molecular dynamics simulation; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2020.107325
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: The main protease of SARS-CoV-2 has a highly flexible active site. Drug repurposing is a treatment opportunity in the current COVID-19 pandemic. Nine drugs merit testing as inhibitors of the SARS-CoV-2 main protease. Abstract: The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide therapeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.