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All Studies   Meta Analysis       

Comparison of the Neutralization Power of Sotrovimab Against SARS-CoV-2 Variants: Development of a Rapid Computational Method

Ashoor et al., JMIR Bioinformatics and Biotechnology, doi:10.2196/58018
Oct 2024  
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Sotrovimab for COVID-19
41st treatment shown to reduce risk in May 2023, now with p = 0.002 from 25 studies, recognized in 38 countries. Efficacy is variant dependent.
Lower risk for mortality, ICU, and hospitalization.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
In Silico computational method developed to predict the neutralization power of monoclonal antibodies against new SARS-CoV-2 variants. The method evaluates binding affinity of antibodies based on molecular interactions and Gibbs free energy compared to a reference model. Analysis of sotrovimab (S309) shows decreased binding affinity to delta and omicron variants compared to the original Wuhan strain. The G339H and G339D mutations are found to play a key role in sotrovimab's reduced neutralization of omicron subvariants, which aligns with published clinical reports.
Ashoor et al., 10 Oct 2024, peer-reviewed, 3 authors. Contact: danana@agu.edu.bh.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperSotrovimabAll
Comparison of the Neutralization Power of Sotrovimab Against SARS-CoV-2 Variants: Development of a Rapid Computational Method
MSc Dana Ashoor, PhD Maryam Marzouq, M Fathallah
JMIR Bioinformatics and Biotechnology, doi:10.2196/58018
Background: The rapid evolution of SARS-CoV-2 imposed a huge challenge on disease control. Immune evasion caused by genetic variations of the SARS-CoV-2 spike protein's 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 anti-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 the spike proteins of the severe acute respiratory syndrome coronavirus (GenBank accession number YP_009825051.1) and SARS-CoV-2 (GenBank accession number YP_009724390.1) were used to create computational 3D models for the native spike proteins. Specific mutations were introduced to the curated sequence to generate the different variant spike models. The neutralization potential of sotrovimab (S309) against these variants was evaluated based on its molecular interactions and Gibbs free energy in comparison to a reference model after molecular replacement of the reference receptor-binding domain with the variant's receptor-binding domain. Results: Our results show a loss in the binding affinity of the neutralizing antibody S309 with both SARS-CoV and SARS-CoV-2. The binding affinity of S309 was greater to the Alpha, Beta, Gamma, and Kappa variants than to the original Wuhan strain of SARS-CoV-2. However, S309 showed a substantially decreased binding affinity to the Delta and Omicron variants. Based on the mutational profile of Omicron subvariants, our data describe the effect of the G339H and G339D mutations and their role in escaping antibody neutralization, which is in line with published clinical 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.
Authors' Contributions DA carried out the in silico analysis, designed the methodology, curated the data, and drafted and edited the manuscript. MM designed the illustrations and figures. M-DF conceptualized the study, analyzed the data, drafted and edited the manuscript, and supervised the study. Conflicts of Interest None declared. Multimedia
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