Mutational characterization of Omicron SARS-CoV-2 lineages circulating in Chhattisgarh, a central state of India

Abstract

Introduction: The emergence of the Omicron SARS-CoV-2 variant from various states of India in early 2022 has caused fear of its rapid spread. The lack of such reports from Chhattisgarh (CG), a central state in India, has prompted us to identify the Omicron circulating lineages and their mutational dynamics.

Materials and methods: Whole-genome sequencing (WGS) of SARS-CoV-2 was performed in 108 SARS-CoV-2 positive combined samples of nasopharyngeal and oropharyngeal swabs obtained from an equal number of patients.

Results: All 108 SARS-CoV-2 sequences belonged to Omicron of clade 21L (84%), 22B (11%), and 22D (5%). BA.2 and its sub-lineages were predominantly found in 93.5% of patients, BA.5.2 and its sub-lineage BA.5.2.1 in 4.6% of patients, and B.1.1.529 in 2% of patients. Various BA.2 sub-lineages identified were BA.2 (38%), BA.2.38 (32%), BA.2.75 (9.25%), BA.2.56, BA.2.76, and BA.5.2.1 (5% each), BA.2.74 (4.6%), BA.5.2.1 (3.7%), BA.2.43 and B.1.1.529 (1.8% each), and BA.5.2 (0.9%). Maximum mutations were noticed in the spike (46), followed by the nucleocapsid (5), membrane (3), and envelope (2) genes. Mutations detected in the spike gene of different Omicron variants were BA.1.1.529 (32), BA.2 (44), BA.2.38 (37), BA.2.43 (38), BA.2.56 (30), BA.2.74 (31), BA.2.75 (37), BA.2.76 (32), BA.5.2, and BA.5.2.1 (38 similar mutations). The spike gene showed the signature mutations of T19I and V213G in the N-terminal domain (NTD), S373P, S375F, T376A, and D405N in receptor-binding domain (RBD), D614G, H655Y, N679K, and P681H at the furin cleavage site, N764K and D796K in fusion peptide, and Q954H and N969K in heptapeptide repeat sequence (HR)1. Notably, BA.2.43 exhibited a novel mutation of E1202Q in the C terminal. Other sites included ORF1a harboring 13 mutations followed by ORF1b (6), ORF3a (2), and ORF6 and ORF8 (1 mutation each).

Conclusion: BA.2 followed by BA.2.38 was the predominant Omicron lineage circulating in Chhattisgarh. BA.2.75 could supersede other Omicron due to its mutational consortium advantage. The periodical genomic monitoring of Omicron variants is thus required for real-time assessment of circulating strains and their mutational-induced severity.

Keywords: BA.2.38; BA.2.75; BA.5; COVID-19; Omicron; SARS-CoV-2.

FIGURE 1

Spectrum of the whole-genome sequences of SARS-CoV-2 (N = 108), in terms of (A) Clades and (B) Pango Lineage, from patients of the state of Chhattisgarh.

FIGURE 2

The phylogenetic distribution of whole-genome sequences of 108 SARS-CoV-2 strains from Chhattisgarh, India, and 30 samples from elsewhere, with the reference sequence of the Wuhan strain.

FIGURE 3

Schematic representation of the mutation pattern in the four structural proteins is shown as a heat map from lowest (white) to highest (purple). (A) The SARS-CoV-2 genomic arrangement, (B) mutation pattern in spike protein, (C) mutation pattern in envelop protein, (D) mutation pattern in membrane protein, and (E) mutation pattern in nucleocapsid protein.

FIGURE 4

Three-dimensional structure and amino acid residue mutations in the spike protein of SARS-COV-2 Omicron variant and their sub-lineages. Wuhan trimeric spike glycoprotein prototype (A) and monomeric spike glycoprotein prototype (B) in which red, blue, and green colors showed the N-terminal domain, receptor-binding domain, and S2 subunit of spike proteins, respectively. The amino acid residue substitution and deletion sites are marked in red color and circle, respectively, in Omicron sub-lineages (C–L).