Reactive force field-based molecular dynamics simulation of the interaction between plasma reactive oxygen species and the receptor-binding domain of the spike protein in the capsid protein of SARS-CoV-2

Abstract

Abstract Under the pressures of the current global pandemic, researchers have been working hard to find a reliable way to suppress infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent the spread of COVID-19. Studies have shown that the recognition and binding of human angiotensin-converting enzyme 2 by the receptor-binding domain (RBD) of the spike protein on the surface of SARS-CoV-2 is a crucial step in viral invasion of human receptor cells, and blocking this process could inhibit the virus from invading normal human cells. Plasma treatment can disrupt the structure of the RBD and effectively block the binding process. However, the mechanism by which plasma blocks recognition and binding is not clear. In this study, the reaction between reactive oxygen species (ROS) in plasma and a molecular model of the RBD was simulated using a reactive molecular dynamics method. The results showed that the destruction of the RBD by ROS was triggered by hydrogen abstraction reactions: O and OH abstracted H atoms from the RBD, while the H atoms of H2O2 and HO2 were abstracted by the RBD. This hydrogen abstraction resulted in the breakage of C–H, N–H, O–H and C=O bonds and the formation of C=C and C=N bonds. The addition reaction of OH increased the number of O–H bonds and caused the formation of C–O, N–O and O–H bonds. The dissociation of N–H bonds led to the destruction of the original peptide bond structure and amino acid residues, changed the type of amino acid residues and caused the conversion of N–C and N=C and C=O and C–O. The simulation partially elucidated the microscopic mechanism of the interaction between ROS in plasma and the capsid protein of SARS-CoV-2, providing theoretical support for the control of SARS-CoV-2 infection by plasma, a contribution to overcoming the global pandemic.