Host adaptation of codon usage in SARS-CoV-2 from mammals indicates potential natural selection and viral fitness

Abstract

SARS-CoV-2 infection, which is the cause of the COVID-19 pandemic, has expanded across various animal hosts, and the virus can be transmitted particularly efficiently in minks. It is still not clear how SARS-CoV-2 is selected and evolves in its hosts, or how mutations affect viral fitness. In this report, sequences of SARS-CoV-2 isolated from human and animal hosts were analyzed, and the binding energy and capacity of the spike protein to bind human ACE2 and the mink receptor were compared. Codon adaptation index (CAI) analysis indicated the optimization of viral codons in some animals such as bats and minks, and a neutrality plot demonstrated that natural selection had a greater influence on some SARS-CoV-2 sequences than mutational pressure. Molecular dynamics simulation results showed that the mutations Y453F and N501T in mink SARS-CoV-2 could enhance the binding of the viral spike to the mink receptor, indicating the involvement of these mutations in natural selection and viral fitness. Receptor binding analysis revealed that the mink SARS-CoV-2 spike interacted more strongly with the mink receptor than the human receptor. Tracking the variations and codon bias of SARS-CoV-2 is helpful for understanding the fitness of the virus in virus transmission, pathogenesis, and immune evasion. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-022-05612-6.

Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts

“…Codon bias is the result of non-random mutational patterns, selectional forces, and genome composition. It is related to the gene expression level [ 12 ], gene length [ 13 ], selective transcription [ 14 ], presence of rare codons [ 15 ], preferred codons [ 16 ], preferred codon pairs [ 17 ], protein properties [ 18 ], mRNA structure [ 19 ] roles of translation efficacy [ 20 ] and accuracy [ 21 ]; accordingly, virus fitness in any host [ 22 ] may be explained. Unfit viruses are attenuated in their infectivity and may serve as a vaccine candidate.…”

Consequences of asymmetric mutational pressure for the dynamic of linear B-cell epitopes repertoire of influenza a virus neuraminidase rearrangement

“…It is thought that a virus would bene t if its codon usage bias is close to the one in the genes of its host [18]. Studies on the comparison of codon usage between different viruses and their hosts are numerous [19,20]. However, such similarities may occur occasionally as well, and it is important to study them on a large scale.…”