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NTD Remodeling in the SARS-CoV-2 BA.3.2 Variant May Influence Spike Stability and Immune Escape
Miriana Quaranta1, Alessandra Ciccozzi2, Francesco Branda3
1Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, 00185 Rome, Italy.
Pathogens (Basel, Switzerland)
|July 28, 2026
Summary
A new SARS-CoV-2 variant, BA.3.2, emerged with significant spike mutations and N-terminal domain remodeling. This variant shows distinct evolutionary dynamics compared to BA.3, highlighting the need for ongoing surveillance.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Omicron BA.3 subvariant descendant BA.3.2 emerged in South Africa in November 2024.
- BA.3.2 exhibits extensive N-terminal domain (NTD) remodeling, including deletions and insertions in the spike protein.
Purpose of the Study:
- Compare evolutionary dynamics and structural features of BA.3.2 with BA.3.
- Investigate the impact of mutations on SARS-CoV-2 evolution and antigenicity.
Main Methods:
- Phylodynamic analyses to assess evolutionary trajectories.
- Selection analyses to identify driven mutations.
- Structural and molecular dynamic analyses of the spike NTD.
Main Results:
- BA.3.2 displays recent emergence and a decreasing effective population size.
- Evolution of BA.3 was driven by receptor-binding domain changes; BA.3.2 shows dispersed signals across spike regions.
- BA.3.2 NTD exhibits increased flexibility and conformational landscape due to deletions and loss of stabilizing interactions.
Conclusions:
- BA.3.2 follows a distinct evolutionary path with significant antigenic remodeling of the spike NTD.
- Continuous surveillance of emerging SARS-CoV-2 descendant lineages is crucial.
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