Molecular Docking and Molecular Dynamics Simulations of Molnupiravir Against Covid-19

Abstract

The most stable conformation of molnupiravir (C13H19N3O7), which is frequently used in the COVID-19 treatment, was elucidated by the Spartan06 program. Using the CAVER program, the potential active binding sites that belong to the spike glycoprotein, ACE2 receptor, and both the apo and holo forms of the main protease enzyme(Mpro) of COVID-19 were identified. To determine the binding affinity of molnupiravir to target receptors, molecular docking analyses were carried out using Autodock Vina. The results of molecular docking calculations of the molnupiravir with the spike glycoprotein (PDB ID:6VXX), ACE2 (PDB ID:6M0J;1R42), the apo form (PDB ID: 6M03) and the holo form of COVID-19 Mpro (PDB ID: 6LU7) showed strong binding affinities at -7.8, -7.7, -7.7, -7.1, and -7.4 kcal/mol, respectively. Moreover, top-scoring ligand-receptor complex of the molnupiravir with ACE2 (1R42) were subjected to 50 ns all-atom MD simulations to investigate the ligand-receptor interactions in more detail.