Molecular mechanism of Ensitrelvir and its similarity inhibiting SARS-CoV-2 main protease by molecular dynamics simulation

Tóm tắt

The unprecedented challenge posed by the COVID-19 pandemic, driven by SARS-CoV-2, has emerged as a global threat. In response, a limited array of therapeutics has been approved for the prevention and treatment of SARS-CoV-2 infection. The main protease (Mpro) of SARS-CoV-2 has been a significant target for drug development efforts because of its crucial role in the viral replication process. This study is to investigate the efficacy of Ensitrelvir and its derivatives in inhibiting the mechanism of the Mpro target of SAR-CoV-2. Docking simulation and molecular dynamic simulation (SMD) techniques were employed for this purpose. The results indicate that the CID 166498740 derivative obtained affinity energy -9.3 kcal/mol and rupture force (F_max) 638.3 ± 79.3 (pN), which proved that the CID 166498740 derivative strongly interacted with the Mpro target, emphasizing non-binding interactions as more crucial than hydrogen bonding in stabilizing the receptor-ligand conformation.