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bioRxiv · 10.1101/2020.11.21.392407

N439K variant in spike protein may alter the infection efficiency and antigenicity of SARS-CoV-2 based on molecular dynamics simulation

Zhou, W.·Xu, C.·Wang, P.·Luo, M.·Xu, Z.·Cheng, R.·Jin, X.·Guo, Y.·Xue, G.·Juan, L.·Nie, H.·Jiang, Q.
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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge which resulted in greater electrostatic complementarity. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. These findings would offer guidance on the development of neutralizing antibodies and the prevention of COVID-19.

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Zhou, W., Xu, C., Wang, P., Luo, M., Xu, Z., Cheng, R., Jin, X., Guo, Y., Xue, G., Juan, L., Nie, H., Jiang, Q.. 2020-11-23. N439K variant in spike protein may alter the infection efficiency and antigenicity of SARS-CoV-2 based on molecular dynamics simulation. https://doi.org/10.1101/2020.11.21.392407

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