Interactive Mechanism of Potential Inhibitors with Glycosyl for SARS-CoV-2 by Molecular Dynamics Simulation

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a type of Ribonucleic Acid (RNA) coronavirus and it has infected and killed many people around the world. It is reported that the receptor binding domain of the spike protein (S_RBD) of the SARS-CoV-2 virus is responsible for attachment to human angiotensin converting enzyme II (ACE2). Many researchers are attempting to search potential inhibitors for fighting SARS-CoV-2 infection using theoretical or experimental methods. In terms of experimental and theoretical research, Cefuroxime, Erythromycin, Lincomycin and Ofloxacin are the potential inhibitors of SARS-CoV-2. However, the interactive mechanism of the protein SARS-CoV-2 and the inhibitors are still elusive. Here, we investigated the interactions between S_RBD and the inhibitors using molecular dynamics (MD) simulations. Interestingly, we found that there are two binding sites of S_RBD for the four small molecules. In addition, our analysis also illustrated that hydrophobic and π-π stacking interactions play crucial roles in the interactions between S_RBD and the small molecules. In our work, we also found that small molecules with glycosyl group have more effect on the conformation of S_RBD than other inhibitors, and they are also potential inhibitors for the genetic variants of SARS-CoV-2. This study provides in silico-derived mechanistic insights into the interactions of S_RBD and inhibitors, which may provide new clues for fighting SARS-CoV-2 infection.