A systematic mutation analysis of 13 major SARS-CoV-2 variants

Area of Science:

• Virology
• Molecular Biology
• Genomics

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continuously evolves with new mutations.
• Understanding the functional impact of these mutations, particularly regarding infectivity, transmissibility, and immune evasion, is critical.
• Previous studies on major SARS-CoV-2 variants have limitations in comprehensive mutation analysis.

Purpose of the Study:

• To systematically analyze mutations, phylogenetic features, physicochemical properties, molecular dynamics, and immune escape across thirteen major SARS-CoV-2 variants.
• To investigate the functional consequences of mutations and the mechanisms of immune evasion conferred by the spike (S) proteins.
• To confirm variant infectivity using pseudotype virus assays.

Main Methods:

• Systematic analysis of full-length amino acid mutations.
• Phylogenetic analysis and protein physicochemical property assessment.
• Molecular dynamics simulations, immune escape site identification, and pseudotype virus infection assays.

Main Results:

• Omicron variant displays the highest number and complexity of mutation sites, with increased hydrophobicity and flexibility.
• Omicron's S protein shows enhanced binding to the ACE2 receptor, indicated by more hydrogen bonds and stronger binding free energy.
• Ten immune escape sites were identified across variants, with four sites (339/373/477/496) newly reported for Omicron and one (462) for Epsilon.

Conclusions:

• The study elucidates the functional consequences of SARS-CoV-2 mutations and the mechanisms behind S protein-mediated immune evasion.
• Findings highlight Omicron's distinct mutational profile and enhanced binding characteristics.
• Identified immune escape sites provide crucial insights for understanding viral evolution and developing countermeasures.