The efficacy of Paxlovid against COVID-19 is the result of the tight molecular docking between Mpro and antiviral drugs (nirmatrelvir and ritonavir)

Purpose: Currently, a number of medications for coronavirus disease 2019 (COVID-19) treatment are tested in clinical trials; however, credible clinical studies are becoming increasingly difficult to come by. Paxlovid is a ritonavir-boosted nirmatrelvir drug that the U.S. Food and Drug Administration (FDA) authorized for the treat-ment of COVID-19. This study aimed to demonstrate the interaction of nirmatrelvir and ritonavir on the active site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). Materials and methods: To locate the optimal docking between Mpro and antiviral drugs, and to conduct dynamic simulations between atoms in the fusion areas, various bioinformatics and mathematical equations were applied. Results: According to the docking data, nirmatrelvir has a stronger interaction with Mpro than ritonavir, which has more multiple bonds. Molecular docking of antiviral drugs such as Paxlovid has a significant impact on the treatment of COVID-19 virus. Conclusions: According to this study, Paxlovid may work on new strains, including Omicron, because the Mpro mutation P132H in the Omicron variant has no direct effect on the protein.