The SARS-CoV-2 S1 spike protein mutation N501Y alters the protein 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
23 Dec 2020 / 18:00 CET
Abstract
The N501Y mutation in Covid-19 arise many question but a small amount of data are currently available. An urgent understanding of N501Y mechanism of action at molecular level is highly required. Here, we present the preliminary results of our Free energy perturbation (FEP) and Molecular dynamics (MD) calculations for the interaction of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody, STE90-C11, derived from COVID-19 patients. The results shown that the S1 RBD-ACE2 interaction was increased whereas those with the STE90-C11 antibody significantly decreased (over about 160 times). This may explain the observed in UK more spread of the virus but also emerge an important question about the possible human immune response and already available vaccines. Indeed, the latter may still act well but our data indicate some possible reduction of their effect. Further studies of N501Y mutation are need
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