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

Ayan Roy,Fucheng Guo,Shelly Gupta,Karan Paul,Bhupender Singh,David M Irwin,Xiaoyuan Chen,Neeta Raj Sharma,Yongyi Shen,Nishika Jaishee

doi:10.3389/fmicb.2021.548275

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading rapidly all over the world and has raised grave concern globally. The present research aims to conduct a robust base compositional analysis of SARS-CoV-2 to reveal adaptive intricacies to the human host. Multivariate statistical analysis revealed a complex interplay of various factors including compositional constraint, natural selection, length of viral coding sequences, hydropathicity, and aromaticity of the viral gene products that are operational to codon usage patterns, with compositional bias being the most crucial determinant. UpG and CpA dinucleotides were found to be highly preferred whereas, CpG dinucleotide was mostly avoided in SARS-CoV-2, a pattern consistent with the human host. Strict avoidance of the CpG dinucleotide might be attributed to a strategy for evading a human immune response. A lower degree of adaptation of SARS-CoV-2 to the human host, compared to Middle East respiratory syndrome (MERS) coronavirus and SARS-CoV, might be indicative of its milder clinical severity and progression contrasted to SARS and MERS. Similar patterns of enhanced adaptation between viral isolates from intermediate and human hosts, contrasted with those isolated from the natural bat reservoir, signifies an indispensable role of the intermediate host in transmission dynamics and spillover events of the virus to human populations. The information regarding avoided codon pairs in SARS-CoV-2, as conferred by the present analysis, promises to be useful for the design of vaccines employing codon pair deoptimization based synthetic attenuated virus engineering.

Highlights

The evolution of viruses is a conundrum for mankind
Our results revealed that the Codon adaptation index (CAI) values of severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV isolated from bats were significantly lower than the CAI values of the respective viral isolates representing the intermediate and human hosts (P < 0.01) (Figure 4)
The recent emergence of the novel SARS-CoV-2 has posed a serious threat to global public health (Benvenuto et al, 2020a)

Summary

Introduction

The evolution of viruses is a conundrum for mankind. High mutation rates and host-shifts have culminated in multiple world-wide pandemics (Mackay and Arden, 2015; Luk et al, 2019). Since December 2019, a viral outbreak by a novel coronavirus, named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged in Wuhan, China, and since. Two other coronavirus have resulted in major outbreaks, the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) in 2002, which resulted in 8,096 cases of infection and 774 deaths, and the Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) in 2012, which infected 2,494 individuals and claimed 858 lives (Lu et al, 2020). The SARS-CoV-2 outbreak has already surpassed both the SARS-CoV and MERS-CoV outbreaks in terms of numbers of infected individuals and numbers of deaths (Lu et al, 2020), the overall case-fatality rate for SARS-CoV-2 appears to be lower than those for both SARS-CoV and MERS-CoV (Wu and McGoogan, 2020)

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Results

Conclusion