Investigation of Nirmatrelvir with Different Crystal Structures Effective on SARS-CoV-2 by In Silico Approaches

Abstract

A pandemic has been declared in the world with the Covid-19 disease caused by the SARS-CoV-2 virus. Scientists on this disease, which is of antiviral origin, have been seeking treatment against SARS-CoV-2 with experimental and computational methods since December 2019. Nirmatrelvir (PF-07321332; NMV), the antiviral component of PAXLOVID™, has been introduced as an inhibitor of the main protease (MPro) of this disease, which is a threat to human health, SARS-CoV- 2. By analyzing the binding interactions between the target and the ligand as in silico with the molecular docking method of Computer Aided Drug Design (CADD), parameters such as amino acids in the binding site, docking score values, binding energy values can be determined. In this study, to six different binding parameters (Docking score, XP GScore, Glide evdw, Glide energy, Glide emodel, MM-GBSA ΔGBind) of Nirmatelvir, an orally taken drug, on the effective crystal structures (7O46, 7QBB, 7NEO, 7B77, 7B2U, 7B2J, 7NBT and 7TVX) of MPro in SARS-CoV-2, were investigated with Schrödinger 2021-2 (Schrödinger, LLC New York, ABD) software. It is presented in this study that different crystal structures have different interactions.