Conserved Pattern and Potential Role of Recurrent Deletions in SARS-CoV-2 Evolution

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• SARS-CoV-2 evolution is driven by mutations and structural variations, complicating COVID-19 control.
• Structural variations, like deletions, have a significant impact on viral genome structure and protein function compared to single nucleotide mutations.

Purpose of the Study:

• To investigate the distribution and frequency of structural variations, specifically deletions, across the entire SARS-CoV-2 genome.
• To identify recurrent deletion regions and assess their potential impact on viral proliferation and host adaptation.
• To analyze the association between deletion patterns and SARS-CoV-2 variants of concern (VOC) and interest (VOI).

Main Methods:

• Genome-wide analysis of deletion patterns in SARS-CoV-2 and related coronaviruses.
• Identification and characterization of recurrent deletion regions (RDRs).
• Frequency analysis of specific deletions and their correlation with viral variants and protein functions.

Main Results:

• 45 recurrent deletion regions were identified in the SARS-CoV-2 genome, with some deletions conferring proliferation advantages.
• Four high-frequency deletions (nsp6 Δ106-109, S Δ69-70, S Δ144, and Δ28271) were found in approximately 50% of genomes.
• Deletions in the spike (S) protein, mainly in the N-terminal domain, were found to block neutralizing antibody binding sites.
• Unique deletion patterns were associated with WHO-defined SARS-CoV-2 variants of concern and interest.

Conclusions:

• Deletions exhibit conserved regional patterns across SARS-CoV-2 and related coronaviruses, suggesting functional importance.
• Specific deletions, particularly in the spike protein's N-terminal domain, can impair antibody neutralization and may influence host adaptation.
• Understanding these structural variations is crucial for effective epidemic control strategies and the development of next-generation vaccines.