26 Dec 2020 Filip Fratev / Micar21

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 Fratev1, 2

1 Micar Innovation (Micar21) Ltd., Persenk 34B, 1407, Sofia, Bulgaria;

2 Department of Pharmaceutical Sciences, School of Pharmacy, The University of Texas at El Paso, 1101 N Campbell St, El Paso, TX 79968, USA;

*Corresponding author e-mail: fratev@micar21.com

26 Dec 2020 / 18:00 CET

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.

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Link to bioRxiv

22 May 2019 Filip Fratev / Micar21 ACS Med. Chem. Lett.2019106904-910

Discovery of New Classes of Glycine transporter 2 (GlyT2) Inhibitors and GlyT2 Selectivity Studies by Combination of Novel Structural Based Virtual Screening Approach and Free Energy Perturbation (FEP+) Calculations

ACS Med. Chem. Lett.2019106904-910

Publication Date:May 22, 2019

https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00003#

Copyright © 2019 American Chemical Society

20 March 2019 Filip Fratev / Micar21 Nature Scientific Reports DOI : 10.1038/s41598-019-53133-1

An Improvement of the Free Energy Perturbation (FEP+) Sampling Protocol in Case of Flexible protein Ligand Binding Sites

20 March 2019 Filip Fratev / Micar21 Journal of Biomolecular, Structure, and Dynamics, Nov 2019 Accepted In press.

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20 April 2018 Filip Fratev / Micar21 / Schrödinger GmbH ACS Omega

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1 November 2017 Filip Fratev / Micar21 Conference: ACS SWRM

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12 February 2016 Filip Fratev / Micar21 Journal of Biomolecular Structure and Dynamics

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8 July 2015 Filip Fratev / Micar21 International Journal of Molecular Sciences

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