Collaborative effects of 2019-nCoV-Spike mutants on viral infectivity

Abstract Background The emerging mutants of the 2019-nCoV coronavirus are posing unprecedented challenges to the pandemic prevention. A thorough, understanding of the mutational characterization responsible for the pathogenic mechanisms of mutations in 2019-nCoV-Spike is indispensable for developing effective drugs and new vaccines. Methods We employed computational methods and viral infection assays to examine the interaction pattern and binding affinity between ACE2 and both single- and multi-mutants of the Spike proteins. Results Using data from the CNCB-NGDC databank and analysis of the 2019-nCoV-Spike/ACE2 interface crystal structure, we identified 31 amino acids that may significantly contribute to viral infectivity. Subsequently, we performed molecular dynamics simulations for 589 single-mutants that emerged from the nonsynonymous substitutions of the aforementioned 31 residues. Ultimately, we discovered 8 single-mutants that exhibited significantly higher binding affinities ( Conclusions These findings will greatly contribute to the future surveillance of viruses and rational design of therapeutics.