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The N501Y and K417N mutations in the spike protein of SARS-CoV-2 alter the interactions with both hACE2 and human derived antibody: A Free energy of perturbation study

View ORCID ProfileFilip Fratev
doi: https://doi.org/10.1101/2020.12.23.424283
Filip Fratev
1Micar Innovation (Micar21) Ltd., Persenk 34B, 1407, Sofia, Bulgaria
2Department of Pharmaceutical Sciences, School of Pharmacy, The University of Texas at El Paso, 1101 N Campbell St, El Paso, TX 79968, USA
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Abstract

The N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise questions but the data about their mechanism of action at molecular level is limited. Here, we present Free energy perturbation (FEP) calculations for the interactions of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results shown that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased; about over 100 times. The K417N mutation had much more pronounced effect and in a combination with N501Y fully abolished the antibody effect. This may explain the observed in UK and South Africa more spread of the virus but also raise an important question about the possible human immune response and the success of already available vaccines.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • We included the K417N mutation in the study and provide new data. The manuscript has been extended. Please use only the data provided in this version. Figure 1A was revised.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 31, 2020.
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The N501Y and K417N mutations in the spike protein of SARS-CoV-2 alter the interactions with both hACE2 and human derived antibody: A Free energy of perturbation study
Filip Fratev
bioRxiv 2020.12.23.424283; doi: https://doi.org/10.1101/2020.12.23.424283
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The N501Y and K417N mutations in the spike protein of SARS-CoV-2 alter the interactions with both hACE2 and human derived antibody: A Free energy of perturbation study
Filip Fratev
bioRxiv 2020.12.23.424283; doi: https://doi.org/10.1101/2020.12.23.424283

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