Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4 and B.1.1.222 or B.1.1.519 and the nucleocapsid mutation S194L associated with symptoms

Abstract

Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1–S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.

Phylogenetic analysis of SARS-CoV-2 viruses circulating in the South American region: Genetic relations and vaccine strain match

“…5 ). Recent studies revealed an association of strains having this substitution and symptomatic patients ( Barona-Gomez et al, 2021 ). Another recent study revealed that one of the most important B and T cell epitope of the N protein lies between residues 305–340 ( Ahmed et al, 2020 ).…”

SARS-CoV-2 Mutations and COVID-19 Clinical Outcome: Mutation Global Frequency Dynamics and Structural Modulation Hold the Key

“…Mutations in the NSP12 region that are involved in RNA-dependent RNA polymerase (RdRp) expression have been shown to contribute toward 5.9 times increased disease severity ( Voss et al., 2020 ). Additionally, the mutation S194L in N protein was reported to be associated with the symptomatic patients and is located in the flexible linker region of the protein N ( Zeng et al., 2020 ; Barona-Gómez et al., 2021 ).…”

An outbreak of SARS-CoV-2 in big hairy armadillos (Chaetophractus villosus) associated with Gamma variant in Argentina three months after being undetectable in humans

“…The non-synonymous mutations identified in Chaetophractus villosus have not been reported previously in other animals infected naturally or experimentally with SARS-CoV-2 Gamma variant. A change in N 194 has been described in human sequences as N_S194L (with a potential association with symptomatic patients (18) but in experimental infections in cats, dogs and mice the change is different (N_S194T) (19). There are no records of ORF6_ I14T and NSP12_ R905K changes in SARS-CoV-2 infected animals.…”