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

Zhang, G.; Liu, H.; Zhang, Q.; Wei, P.; Chen, Z.; Aviszus, K.; Yang, J.; Downing, W.; Peterson, S.; Jiang, C.; Liang, B.; Reynoso, L.; Downey, G.; Frankel, S.; Kapper, J.; Marrack, P.

doi:10.1101/2021.02.02.428884

bioRxiv · 10.1101/2021.02.02.428884

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

Zhang, G.·Liu, H.·Zhang, Q.·Wei, P.·Chen, Z.·Aviszus, K.·Yang, J.·Downing, W.·Peterson, S.·Jiang, C.·Liang, B.·Reynoso, L.·Downey, G.·Frankel, S.·Kapper, J.·Marrack, P.

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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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Zhang, G., Liu, H., Zhang, Q., Wei, P., Chen, Z., Aviszus, K., Yang, J., Downing, W., Peterson, S., Jiang, C., Liang, B., Reynoso, L., Downey, G., Frankel, S., Kapper, J., Marrack, P.. 2021-02-02. The basis of a more contagious 501Y.V1 variant of SARS-COV-2. https://doi.org/10.1101/2021.02.02.428884

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