Molecular docking assessment of clinically approved antiviral drugs against MPRO, spike glycoprotein and angiotensin converting enzyme-2 revealed probable anti-SARS-CoV-2 potential

Abstract

Ever since the novel SARS-CoV-2 coronavirus was identified at Wuhan in China, numerous researchers have been working on remedies to ameliorate the COVID-19 disease perpetrated by this deadly virus. Umpteen researchers engaged in silico approaches as a fast means of discovering drugs with potential inhibitory activity against SARS-CoV-2 to combat the COVID-19 pandemic. In this computational study, FDA approved antiretroviral, anti-Ebola, and anti-SARS drugs were docked against SARS-COV-2 Mpro (6LU7), Prefusion 2019-nCoV Spike glycoprotein (6VSB), the peptidase domain of human ACE2 (2AJF) and SARS-CoV 3CL protease (2ZU4) in order to detect the drugs with the best binding affinity for the active sites of these proteins. The top 3 drugs for each class of drugs show strong binding affinities from-7.5--9.2 Kcal/mol. The docking result shows the consistent score of Saquinavir, Amodiaquine, Clomiphene, Indinavir, Lopinavir, Maraviroc, Nelfinavir, and Verapamil across those proteins. However, our results indicate that indinavir, saquinavir and maraviroc with considerable binding affinity might be further optimized in preclinical and clinical studies to determine their role in the management of COVID-19. Furthermore, we noticed that the amino acid residues common to 6LU7-ligand complexes and 2ZU4-ligand complexes include Glu166, Cys145, and Met49. We therefore conclude that these residues could be critical to their functional and catalytic potentials. These residues could also be a critical component of their conserved domain that forms catalytic dyad because our result falls in line with others where His41 and Cys145 were reported to be conserved residues at Mpro active site.