SARS-CoV-2 main protease-nirmatrelvir and molnupiravir molecular dynamic simulations of complex structures

The SARS-CoV-2 Mpro enzyme is considered an important drug target as it is involved in the viral replication and spread of the SARS-CoV-2 virus. In this study, the effects of Nirmatrelvir and Molnupiravir ligands on the conformational and dynamic structure of SARS-CoV-2 Mpro were investigated using molecular dynamics simulations. The results showed that active sites interact in SARS-CoV-2 Mpro structures and Nirmatrelvir was found to be an asymmetric inhibitor. On the other hand, Molnupiravir was shown to be a symmetric inhibitor with similar effects on both chains of SARS-CoV-2 Mpro. Additionally, it was demonstrated that the structure of SARS-CoV-2 Mpro is stable, and the Nirmatrelvir-SARS-CoV-2 Mpro and Molnupiravir-SARS-CoV-2 Mpro complexes exhibit different dynamics. In conclusion, Nirmatrelvir and Molnupiravir induce significant changes in the dynamics of SARS-CoV-2 Mpro without causing significant changes on its conformational structure. It is thought that this study will contribute to the designing and development of potent inhibitors targeting SARS-CoV-2 Mpro.