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Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay |
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| Authors: | Ting Xue Weikun Wu Ning Guo Chengyong Wu Jian Huang Lipeng Lai Hong Liu Yalun Li Tianyuan Wang Yuxi Wang |
| Institution: | Targeted Tracer Research and Development Laboratory, Precision Medicine Research Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041 P. R. China.; XtalPi AI Research Center, 7F, Tower B, Dongsheng Building, No. 8, Zhongguancun East Road, Haidian District, Beijing 100083 P. R. China, |
| Abstract: | The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to the 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 results show 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 the in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit the development of broadly neutralizing vaccine and antibody.The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates viral cell attachment and serves as a promising target for therapeutics development. |
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