Evidence of Increased Adaptation of Omicron SARS-CoV-2 Codons to Humans

Viruses are highly dependent on their hosts to carry out cellular mechanisms and cause productive infection. Thus, they undergo extensive adaptations to the host intracellular machinery, which occur over the evolution of the virus, and during the emergence of new viral strains with different properties. One aspect of viral adaptation is related to the efficiency of recruiting the host’s gene expression machinery and specifically the translation machinery. This process can be partially detected using measures of codon usage bias (CUB). While previous studies in the field suggested that there is an adaptation of codons in the viral genome to the host, none of them studied these adaptations among the different strains of the same virus over time. Thus, in this study, we focused on the SARS-CoV-2 and demonstrated for the first time that the omicron strain has an increased codon usage adaptation to humans in the early gene ORF1ab compared to previous strains. In addition, our findings indicate that the observed differences in CUB scores were primarily attributed to non-synonymous mutations. This conclusion holds for additional human-infecting viruses.