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[Preprint]. 2021 Feb 2:2021.02.02.428884. [Version 1] doi: 10.1101/2021.02.02.428884

The basis of a more contagious 501Y.V1 variant of SARS-COV-2

Haolin Liu, Qianqian Zhang, Pengcheng Wei, Zhongzhou Chen, Katja Aviszus, John Yang, Walter Downing, Shelley Peterson, Chengyu Jiang, Bo Liang, Lyndon Reynoso, Gregory P Downey, Stephen K Frankel, John Kappler, Philippa Marrack, Gongyi Zhang
PMCID: PMC7872372  PMID: 33564771

Abstract

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing a world-wide pandemic. A variant of SARS-COV-2 (20I/501Y.V1) recently discovered in the United Kingdom has a single mutation from N501 to Y501 within the receptor binding domain (Y501-RBD), of the Spike protein of the virus. This variant is much more contagious than the original version (N501-RBD). We found that this mutated version of RBD binds to human Angiotensin Converting Enzyme 2 (ACE2) a ~10 times more tightly than the native version (N501-RBD). Modeling analysis showed that the N501Y mutation would allow a potential aromatic ring-ring interaction and an additional hydrogen bond between the RBD and ACE2. However, sera from individuals immunized with the Pfizer-BioNTech vaccine still efficiently block the binding of Y501-RBD to ACE2 though with a slight compromised manner by comparison with their ability to inhibit binding to ACE2 of N501-RBD. This may raise the concern whether therapeutic anti-RBD antibodies used to treat COVID-19 patients are still efficacious. Nevertheless, a therapeutic antibody, Bamlanivimab, still binds to the Y501-RBD as efficiently as its binds to N501-RBD.

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