Base Composition and Host Adaptation of the SARS-CoV-2: Insight From the Codon Usage Perspective

Area of Science:

• Genomics
• Virology
• Bioinformatics

Background:

• The rapid global spread of SARS-CoV-2 necessitates understanding its adaptation to the human host.
• Viral genome composition influences host interaction and pathogenicity.

Purpose of the Study:

• To perform a comprehensive base compositional analysis of SARS-CoV-2.
• To elucidate the adaptive mechanisms of SARS-CoV-2 in the human host.
• To identify potential targets for vaccine development.

Main Methods:

• Multivariate statistical analysis of SARS-CoV-2 genomic sequences.
• Assessment of factors influencing codon usage patterns, including compositional bias, natural selection, sequence length, hydropathicity, and aromaticity.
• Comparative analysis with other coronaviruses (MERS-CoV, SARS-CoV) and viral isolates from different hosts.

Main Results:

• Compositional bias is a critical determinant of codon usage in SARS-CoV-2.
• UpG and CpA dinucleotides are preferred, while CpG dinucleotides are significantly avoided, consistent with human host patterns and potentially linked to immune evasion.
• SARS-CoV-2 exhibits a lower degree of adaptation compared to MERS-CoV and SARS-CoV, possibly correlating with its milder clinical presentation.
• Enhanced adaptation is observed in viral isolates from intermediate and human hosts compared to bat reservoir isolates, highlighting the role of intermediate hosts in spillover.

Conclusions:

• SARS-CoV-2 employs specific compositional strategies, including CpG avoidance, for adaptation and immune evasion in humans.
• The degree of viral adaptation may influence clinical severity.
• Understanding codon pair usage provides a basis for developing novel vaccine strategies, such as codon pair deoptimization for synthetic attenuated virus engineering.