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

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.

Automated summary

Research shows that the RBD of the SARS-CoV-2 virus S protein plays a key role in viral cell attachment, and mutations may affect the potency of vaccines and antibodies. Using in silico methods, the study predicted the impact of RBD mutations on its binding affinity to cell receptors, with experimental results showing agreement with the predictions. This demonstrates the potential of in silico tools in forecasting more powerful virus mutants to aid in the development of broadly neutralizing vaccines and antibodies.