Codon Usage and Phenotypic Divergences of SARS-CoV-2 Genes

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2.

Characterization of Codon Usage Pattern in SARS-CoV-2

“…Thus, most codons of SARS-CoV-2 Wuhan-Hu-1 tended to be U ending. Moreover, the mean GC and AU compositions (Supplementary Figure 1B) were 37.9% and 62.1% (SARS-CoV-2 Wuhan-Hu-1), 41.0% and 59.0% (SARS-CoV Tor2), 40.8% and 59.2% (SARS-CoV Urbani), 41.5% and 58.5% (MERS-CoV HCoV-EMC), 36.8% and 63.2% (HCoV-OC43), 32.0% and 68.0% (HCoV-HKU1), 38.0% and 62.0% (HCoV-229E), 34.4% and 65.6% (HCoV-NL63), respectively indicating that SARS-CoV-2 Wuhan-Hu-1 as well as other human coronaviruses in this study were all AU rich, which was consistent with recent reports [11][12][13][14][15].…”

“…Additionally, the overall codon usage pattern of SARS-CoV-2 was generally similar to that of its phylogenetic relatives among non-human coronaviruses such as RaTG13. Our ndings are consistent with the recent observations [11][12][13][14][15] and provide new insights into the characteristics of codon usage pattern in coronaviruses. These results also have important implications for future work.…”

Comprehensive analysis of synonymous codon usage patterns and influencing factors of porcine epidemic diarrhea virus

“…Compared with the mean ENC value for PEDV in the first report published six year ago (47.91 ± 0.13) [ 11 ], the latest data changed little, with a small standard deviation. Of note, the ENC mean value of SARS-CoV-2 has been reported to be 51.90 ± 2.59 (mean ± SD) [ 31 ], which is higher than that of most coronaviruses, suggesting that it is well adapted to its host and able to overcome its defense mechanisms.…”

Low‐dose radiation as a treatment for COVID‐19 pneumonia: A threat or real opportunity?

“…... 6 In addition, as discussed in a recent manuscript, 4 any antiviral drug treatment against SARS-CoV-2 would probably result in a more intense selective pressure on the virus. Moreover Dilucca et al 7 in their paper published recently in the Viruses Journal highlight the importance of LDRT and address the potential problems associated with the widespread use of different antiviral drugs as discussed in a recent paper, 4 any antiviral drug against SARS-CoV-2 would exert an intense selective pressure on the virus. This may result in highly adaptive and treatment-resistant virus types with enhanced pathogenicity.…”