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Since the start of the coronavirus disease 2019 (COVID‐19) pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly widespread worldwide becoming one of the major global public health issues of the last centuries. Currently, COVID‐19 vaccine rollouts are finally upon us carrying the hope of herd immunity once a sufficient proportion of the population has been vaccinated or infected, as a new horizon. However, the emergence of SARS‐CoV‐2 variants brought concerns since, as the virus is exposed to environmental selection pressures, it can mutate and evolve, generating variants that may possess enhanced virulence. Codon usage analysis is a strategy to elucidate the evolutionary pressure of the viral genome suffered by different hosts, as possible cause of the emergence of new variants. Therefore, to get a better picture of the SARS‐CoV‐2 codon bias, we first identified the relative codon usage rate of all  Betacoronaviruses  lineages. Subsequently, we correlated putative cognate transfer ribonucleic acid (tRNAs) to reveal how those viruses adapt to hosts in relation to their preferred codon usage. Our analysis revealed seven preferred codons located in three different open reading frame which appear preferentially used by SARS‐CoV‐2. In addition, the tRNA adaptation analysis indicates a wide strategy of competition between the virus and mammalian as principal hosts highlighting the importance to reinforce the genomic monitoring to prompt identify any potential adaptation of the virus into new potential hosts which appear to be crucial to prevent and mitigate the pandemic.

Betacoronaviruses genome analysis reveals evolution toward specific codons usage: Implications for SARS‐CoV‐2 mitigation strategies