Abstract

SARS-CoV-2 is the pathogen responsible for COVID-19 that has claimed over six million lives as of July 2022. The severity of COVID-19 motivates a need to understand how it could evolve to escape potential treatments and to find ways to strengthen existing treatments. Here, we used the molecular modeling methods MD + FoldX and PyRosetta to study the SARS-CoV-2 spike receptor binding domain (S-RBD) bound to two neutralizing antibodies, B38 and CB6 and generated lists of antibody escape and antibody strengthening mutations. Our resulting watchlist contains potential antibody escape mutations against B38/CB6 and consists of 211/186 mutations across 35/22 S-RBD sites. Some of these mutations have been identified in previous studies as being significant in human populations (e.g., N501Y). The list of potential antibody strengthening mutations that are predicted to improve binding of B38/CB6 to S-RBD consists of 116/45 mutations across 29/13 sites. These mutations could be used to improve the therapeutic value of these antibodies.

Details

Title
The effect of mutations on binding interactions between the SARS-CoV-2 receptor binding domain and neutralizing antibodies B38 and CB6
Author
Barnes, Jonathan E. 1 ; Lund-Andersen, Peik K. 2 ; Patel, Jagdish Suresh 2 ; Ytreberg, F. Marty 3 

 University of Idaho, Institute for Modeling Collaboration and Innovation, Moscow, USA (GRID:grid.266456.5) (ISNI:0000 0001 2284 9900) 
 University of Idaho, Institute for Modeling Collaboration and Innovation, Moscow, USA (GRID:grid.266456.5) (ISNI:0000 0001 2284 9900); University of Idaho, Department of Biological Sciences, Moscow, USA (GRID:grid.266456.5) (ISNI:0000 0001 2284 9900) 
 University of Idaho, Institute for Modeling Collaboration and Innovation, Moscow, USA (GRID:grid.266456.5) (ISNI:0000 0001 2284 9900); University of Idaho, Department of Physics, Moscow, USA (GRID:grid.266456.5) (ISNI:0000 0001 2284 9900) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2732139380
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.