How SARS-CoV-2 Omicron spike mutations contribute to increased infectivity

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How SARS-CoV-2 Omicron spike mutations contribute to increased infectivity
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How SARS-CoV-2 Omicron spike mutations contribute to increased infectivity SARSCoV2 Omicron SpikeProtein COVID neutralization BA1 BA2 variant evolution cellhostmicrobe uni_ulm TheCrick

By Neha MathurJul 25 2022Reviewed by Benedette Cuffari, M.Sc. In a recent Cell Host and Microbe study, researchers introduce spike mutations found in the severe acute respiratory syndrome coronavirus 2 Omicron variant into the S protein of the SARS-CoV-2 ancestral Wuhan-Hu 1 strain to study the functional impact of these mutations.

Related StoriesOnly about 13% of the SARS-CoV-2 genome encodes for the S protein. Nevertheless, the Omicron S protein contains the greatest number of mutations as compared to other SARS-CoV-2 variants. All current COVID-19 vaccines are based on the SARS-CoV-2 Wuhan-Hu 1 S antigen. As a result, mutations in the NTD or RBD of the Omicron S could increase the resistance of these strains to neutralizing antibodies . These mutations may also be crucial determinants of the higher transmissibility and reduced pathogenicity of these variants.Graphical abstract

The researchers also used full-length S proteins containing a simian virus 5 epitope tag for analysis of Omicron S expression and processing. Several assays were also performed to quantify the number of VSVpp infected Caco-2 cells over time. Mutations in the three serine residues of S371, S373, and S375 severely impaired the ability of the Wuhan Hu-1 S protein to mediate virus-cell and cell-cell fusion. Furthermore, the S371L, S373P, and S375F AA mutated residues promoted interprotomer interactions between the “down” RBDs.

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