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. 2022 Mar:26:101537.
doi: 10.1016/j.genrep.2022.101537. Epub 2022 Feb 2.

Highlight of potential impact of new viral genotypes of SARS-CoV-2 on vaccines and anti-viral therapeutics

Affiliations

Highlight of potential impact of new viral genotypes of SARS-CoV-2 on vaccines and anti-viral therapeutics

Abozar Ghorbani et al. Gene Rep. 2022 Mar.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the coronavirus disease (COVID-19) pandemic, has infected millions of people globally. Genetic variation and selective pressures lead to the accumulation of single nucleotide polymorphism (SNP) within the viral genome that may affect virulence, transmission rate, viral recognition and the efficacy of prophylactic and interventional measures. To address these concerns at the genomic level, we assessed the phylogeny and SNPs of the SARS-CoV-2 mutant population collected to date in Iran in relation to globally reported variants. Phylogenetic analysis of mutant strains revealed the occurrence of the variants known as B.1.1.7 (Alpha), B.1.525 (Eta), and B.1.617 (Delta) that appear to have delineated independently in Iran. SNP analysis of the Iranian sequences revealed that the mutations were predominantly positioned within the S protein-coding region, with most SNPs localizing to the S1 subunit. Seventeen S1-localizing SNPs occurred in the RNA binding domain that interacts with ACE2 of the host cell. Importantly, many of these SNPs are predicted to influence the binding of antibodies and anti-viral therapeutics, indicating that the adaptive host response appears to be imposing a selective pressure that is driving the evolution of the virus in this closed population through enhancing virulence. The SNPs detected within these mutant cohorts are addressed with respect to current prophylactic measures and therapeutic interventions.

Keywords: ACE2, Angiotensin-converting enzyme 2; Antiviral drugs; Bioinformatics; CSSE, Center for Systems Science and Engineering; E, Envelope; FP, Fusion peptide; HR1, Heptad repeat 1; HR2, Heptad repeat 2; IC, Intracellular domain; JHU, Johns Hopkins University; M, Membrane; Mutation detection; N, Nucleocapsid; NAG, N-acetylglucosamine; NSP, Non-structural proteins; NTD, N-terminal domain; Phylogenetic analysis; RBD, Receptor-binding domain; S, Spike glycoprotein; SARS-CoV-2; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2;; SD1, Subdomain 1; SD2, Subdomain 2; SNP, Single nucleotide polymorphism; SP, Structural proteins; TM, Transmembrane region; UTRs, Untranslated regions; Viral vaccines.

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Conflict of interest statement

The authors declare that they have no conflict of interest. The research reported here did not involve experimentation with human participants or animal.

Figures

Fig. 1
Fig. 1
Position of SNPs on the 3D structure of SARS-CoV-2 Spike protein in Iranian isolates. SNPs have been shown in green color. A, B, and C show SNPs in a chain. D show SNPs in a chain that combined to other two chains. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 2
Fig. 2
Location of SNPs in the binding site of N-acetylglucosamine and polysorbate 80 with spike protein of SARS-CoV-2, Iranian isolates.
Fig. 3
Fig. 3
The whole genome-based phylogenetic analysis of SARS-CoV-2 isolates from Iran and other countries and a candidate of new variants.

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