A study on non-synonymous mutational patterns in structural proteins of SARS-CoV-2

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• The emergence of SARS-CoV-2 variants necessitates understanding viral mutations for host adaptation and infection dynamics.
• Amino acid substitutions in viral proteins are key indicators of viral evolution and biological behavior.

Purpose of the Study:

• To investigate amino acid substitutions in SARS-CoV-2 structural proteins.
• To characterize protein-wise variants, substitution patterns, and major changes across global sequences.
• To identify mutations impacting viral function and host interaction.

Main Methods:

• Analysis of 9587 SARS-CoV-2 structural protein sequences from 49 countries.
• Characterization of protein-specific variants, substitution types, locations, and biochemical property changes.
• Identification of co-occurring substitutions and mutations in critical protein domains.

Main Results:

• Majority of substitutions were unique, location-specific, and altered amino acid biochemical properties.
• Envelope (E) and Membrane (M) proteins showed higher stability compared to Nucleocapsid (N) and Spike (S) proteins.
• Significant mutations were observed in S protein (heptapeptide repeat, fusion peptides, transmembrane domains) and N protein (N-terminal, C-terminal domains), including deleterious ones.

Conclusions:

• SARS-CoV-2 structural proteins exhibit considerable sequence diversity, particularly S and N proteins, with notable co-occurrence of substitutions.
• Mutations in key functional domains of S and N proteins suggest potential impacts on viral biology and host adaptation.
• The study highlights the dynamic nature of SARS-CoV-2 evolution at the genomic level early in the pandemic.