Mutational cascade of SARS-CoV-2 leading to evolution and emergence of omicron variant

Abstract

Background: Emergence of new variant of SARS-CoV-2, namely omicron, has posed a global concern because of its high rate of transmissibility and mutations in its genome. Researchers worldwide are trying to understand the evolution and emergence of such variants to understand the mutational cascade events. Methods: We have considered all omicron genomes (n = 302 genomes) available till 2nd December 2021 in the public repository of GISAID along with representatives of variants of concern (VOC), i.e., alpha, beta, gamma, delta, and omicron; variant of interest (VOI) mu and lambda; and variant under monitoring (VUM). Whole genome-based phylogeny and mutational analysis were performed to understand the evolution of SARS CoV-2 leading to emergence of omicron variant. Results: Whole genome-based phylogeny depicted two phylogroups (PG-I and PG-II) forming variant specific clades except for gamma and VUM GH. Mutational analysis detected 18,261 mutations in the omicron variant, majority of which were non-synonymous mutations in spike (A67, T547K, D614G, H655Y, N679K, P681H, D796Y, N856K, Q954H), followed by RNA dependent RNA polymerase (rdrp) (A1892T, I189V, P314L, K38R, T492I, V57V), ORF6 (M19M) and nucleocapsid protein (RG203KR). Conclusion: Delta and omicron have evolutionary diverged into distinct phylogroups and do not share a common ancestry. While, omicron shares common ancestry with VOI lambda and its evolution is mainly derived by the non-synonymous mutations.

Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines

“…The Omicron variant of the SARS‐CoV‐2 genome constitutes 18 261 mutations from which more than 97% mutations are present in the coding region, and the remaining 558 are detected in the extragenic region. 11 Mutations in the coding region are 2965 indels and nonsynonymous, and synonymous single‐nucleotide polymorphisms (SNPs) mutations are 11 995 and 2743, respectively. 11 Thirty mutations have been found within the spike proteins mostly located at the receptor‐binding domain (RBD) of the spike protein of the Omicron variant (Figure 1 ).…”

“… 11 Mutations in the coding region are 2965 indels and nonsynonymous, and synonymous single‐nucleotide polymorphisms (SNPs) mutations are 11 995 and 2743, respectively. 11 Thirty mutations have been found within the spike proteins mostly located at the receptor‐binding domain (RBD) of the spike protein of the Omicron variant (Figure 1 ). 12 For more than 270 million reported SARS‐CoV‐2 infections worldwide, the virus has evolved into over 1500 distinct Pango lineages.…”

Omicron: What Makes the Latest SARS-CoV-2 Variant of Concern So Concerning?

“…What is alarming is the distribution of mutations, with about 30 of them being located in the viral Spike gene that is critical for virus infection and the key target of protective immune responses. In addition, most nucleotide changes distinguishing the Omicron VOC from the early Wuhan Hu-1 strain are nonsynonymous ( 37 ), i.e., associated with amino acid changes, suggesting high positive selection pressure for change. Meanwhile, almost half a million Omicron sequences are available at the GISAID database, revealing significant diversification.…”

Molnupiravir (MK-4482) is efficacious against Omicron and other SARS-CoV-2 variants in the Syrian hamster COVID-19 model

“…Thus, MK-4482 remains a potent alternative to monoclonal antibody treatment which is rather vulnerable to mutations in the spike protein ( 8 ). Although Omicron already has mutations in the viral polymerase protein ( 15 ), the target of MK-4482 antiviral action, the drug remains effective against this VOC with significant reduction of viral replication in the upper and lower respiratory tract. It remains to be seen whether future variants that may develop under more widespread clinical use of molnupiravir will acquire further mutations in the polymerase resulting in reduced drug activity or even loss of drug efficacy.…”