Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay

Xue, Ting; Wu, Weikun; Guo, Ning; Wu, Chengyong; Huang, Jian; Lai, Lipeng; Liu, Hong; Li, Yalun; Wang, Tianyuan; Wang, Yuxi

The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates the viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to cell receptor and affect the potency of vaccines and antibodies. Here we used an in-silico approach to predict how mutations on RBD affect its binding affinity to hACE2 (human angiotensin-converting enzyme2). The effect of all single point mutations on the interface was predicted. SPR assay result shows that 6 out of 9 selected mutations can strengthen binding affinity. Our prediction has reasonable agreement with the previous deep mutational scan results and recently reported mutants. Our work demonstrated in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit for the development of broadly neutralizing vaccine and antibody.