Interaction mechanism of cold atmospheric plasmas and fusion peptides of spike protein in SARS-CoV-2 revealed by reactive molecular dynamics simulation

Despite the conclusion of the COVID-19 pandemic, the coronavirus-killing ability of cold atmospheric plasma (CAP) remains impressive, and investigations into its underlying mechanisms are still ongoing. The fusion peptide (FP) is a crucial site of membrane fusion and toxicity exerted by the S-protein in severe acute respiratory syndrome CoV-2 (SARS-CoV-2). In this study, reactive molecular dynamics simulations were performed to investigate the interaction mechanisms of FP and reactive oxygen species (ROS). The simulation results show that the given ROS (O atoms and OH radicals as examples) can destroy hydrophobic residues, negatively charged acidic residues, and peptide bonds through structurally altering essential sites. Furthermore, the reaction typically initiates from the H-abstraction reaction, followed by various types of oxidative modifications such as dehydrogenation, hydroxylation, carbonylation, cyclogenesis, ring cleavage, and decarboxylation, which are consistent with the experimental findings made on peptides. Therefore, it can be predicted that the membrane fusion ability of FP and the toxicity of SARS-CoV-2 will be reduced, with CAP functioning as a bactericidal disinfectant. The dose effects were also investigated, providing experimental guidance for the optimization of CAP. In this study, the interaction processes of FP and CAP are explored by revealing the chemical pathways and final reaction products from the computational data, thus providing a fundamental understanding of the mechanisms for inactivating SARS-CoV-2 by CAP.