Comparative Analysis of Codon Usage, Rare Codon Clusters and Phylogenetic Relations of COVID-19, SARS, and MERS

Coronaviruses are enveloped single-stranded RNA genome viruses causing respiratory distress syndromes. The aim of this study was to compare codon usage, rare codon clusters and phylogenetic relations in orf1a polyprotein of COVID-19, SARS, and MERS coronaviruses. The frequency, number and fraction of 61 codons for each amino acid was evaluated in the structure of viral protein and the preferred codons were assessed using Gene Infinity website. The variations in codon usage bias were quantified by the ENC and CBI in the ACUA software. Finally, evolutionary relationship and phylogenetic analysis of Coronaviridae were studied using the MEGA 7 software. The GC3% of the cds was in the range from 15.668 to 16.534 and GC3 Skewness from 0.299 to 0.34. Analysis of codon usage for all of amino acid in SARS, MERS and COVID-19 showed considerable differences between three viruses. The close proximity of COVID-19 and SARS in the tree diagram represented a similarity in their gene sequence of orf1a polyprotein (pp1a). This phylogenetic analysis also indicated that COVID-19 and SARS had the near phylogenetic relation based on the nucleotide sequences of orf1a polyprotein in comparison to MERS. The findings of the present study revealed that the patterns of base compositions in COVID-19 are most likely the result of mutation pressure rather than that of natural selection, since at all codon positions its effects are present. In addition, analysis of base composition it was found that the cds of COVID-19 are rich in AT, which should be considered in designing new drugs.