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Adaptive variations in SARS-CoV-2 spike proteins: effects on distinct virus-cell entry stages
1Department of Microbiology and Immunology, Loyola University Chicago , Maywood, Illinois, USA.
Mbio
|June 29, 2023
Summary
Omicron SARS-CoV-2 variants show increased sensitivity to cell entry factors due to spike protein mutations. These changes enhance viral transmissibility and infectivity, offering insights into future variant evolution.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- SARS-CoV-2 variants of concern (VOCs) evolve rapidly, with significant mutations in the spike (S) protein.
- Omicron VOCs exhibit numerous S protein mutations compared to ancestral strains, impacting viral properties.
Purpose of the Study:
- To compare the functional differences in S protein-mediated virus entry between ancestral D614G and Omicron BA.1 SARS-CoV-2 variants.
- To identify specific S protein mutations and domains responsible for altered entry functions in Omicron variants.
Main Methods:
- Utilized cell-free assays to analyze distinct steps of S protein-directed virus entry.
- Constructed domain-exchanged D614G/Omicron recombinants to map functional alterations to specific S protein domains.
Main Results:
- Omicron BA.1 S proteins demonstrated hypersensitivity to receptor activation and proteases, facilitating entry.
- Identified specific S protein domains and inter-domain interactions contributing to enhanced entry efficiency.
- Mapped three key functional alterations to distinct S protein domains.
Conclusions:
- Omicron VOCs possess S protein adaptations that enhance sensitivity to cellular entry factors, promoting increased transmissibility and infectivity.
- The study provides a structure-function atlas of S protein variations, crucial for understanding SARS-CoV-2 evolution and predicting future variants.
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