Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies

Abstract

Vaccination against SARS-CoV-2 just started in most of the countries. However, the development of specific vaccines against SARS-CoV-2 is not the only approach to control the virus and monoclonal antibodies (mAbs) start to merit special attention as a therapeutic option to treat COVID-19 disease. Here, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein of SARS-CoV-2 (S protein) with two mAbs (CR3022 and S309) and the ACE2 cell receptor are studied as the main representatives of three different epitopes on the RBD of S protein. The combined approach of 1 µs accelerated molecular dynamics (aMD) and ab-initio hybrid molecular dynamics is used to identify the most predominant interactions under physiological conditions. Results allow to determine the main receptor-binding mapping, hydrogen bonding network and salt bridges in the most populated antigen-antibody interface conformations. The deep knowledge on the protein-protein interactions involving mAbs and ACE2 receptor with the spike glycoprotein of SARS-CoV-2 increases background knowledge to speed up the development of new vaccines and therapeutic drugs.