Currently accepted at: JMIR Bioinformatics and Biotechnology
Date Submitted: Mar 4, 2024
Open Peer Review Period: Mar 8, 2024 - May 3, 2024
Date Accepted: Apr 19, 2024
(currently open for review)
This paper has been accepted and is currently in production.
It will appear shortly on 10.2196/58018
The final accepted version (not copyedited yet) is in this tab.
A computational method for anti-SARS-CoV-2 antibodies neutralization power: A blueprint with monoclonal antibody Sotrovimab
ABSTRACT
Background:
The rapid evolution of SARS-CoV-2 imposed a huge challenge on disease control. Immune escape caused by genetic variations of SARS-CoV-2 S protein immunogenic epitopes affects the efficiency of monoclonal antibody-based therapy of COVID-19. Therefore, a rapid method is needed to evaluate the efficacy of the available monoclonal antibodies against the new emerging variants or potential novel variants.
Objective:
The aim of this study is to develop a rapid computational method to evaluate the neutralization power of SARS-Cov-2 monoclonal antibodies against new SARS-CoV-2 variants and other potential new mutations.
Methods:
The amino acid sequence of the extracellular domain of SARS-CoV (YP_009825051.1) and SARS-CoV-2 (YP_009724390.1) spike proteins were used to create computational 3D models for the native spike proteins. Specific mutations were introduced to the collected sequence to generate the different variant spike models. Neutralization potential of S309 against theses variants was evaluated based on the molecular interactions and binding energy (ΔG) in comparison to a reference model after molecular replacement of the reference RBD with the variant’s RBD.
Results:
The results showed a loss in binding affinity of the neutralizing antibody S309 with both SARS-CoV and - SARS-CoV-2. Comparing SARS-CoV-2 variants to the binding affinity of the first Wuhan strain showed an improvement of the binding affinity of S309 with variants Alpha, Beta, Gamma and Kappa. However, Delta and Omicron variants showed a substantial decrease in the binding affinity. Based on mutational profile of Omicron subvariants, our data describe the effect of G339H and G339D mutation and its role in escaping antibody neutralization which came in consistent with clinical published reports.
Conclusions:
This method is rapid, applicable and of interest to adapt the use of therapeutic antibodies to the treatment of emerging variants. It could be applied to antibody-based treatment of other viral infections. Clinical Trial: N/A
Citation
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