S5/BA.2.12 and S8/BA.5.2 showed high genetic relatedness, while S2/BA.5.2 was divergent from the other six lineages Parathyroid Hormone (1-34), bovine (Physique 1). in spike region were observed in all the lineages. Furthermore, we identified common mutations of Omicron variants of SARS-CoV-2 in therapeutic hot spot spike region: T19I, D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, A653V, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K, D1146D, L452R, F486V, N679K and D796Y. The effect of RBD-targeted mutations on neutralizing (NAbs) binding was considerable. Conclusion The outcome of this first report on SARS-CoV-2 variants identification and mutation in the Al-Baha region could be used to lay down the policies to manage and impede the regional outbreak of COVID-19 effectively. Keywords: omicron, SARS-CoV-2, nextstrain clade, phylogeny, mutation, spike, RBD Introduction SARS-CoV-2 is the most lethal virus among all human coronavirus (HCoV) and is responsible for causing severe respiratory tract infections.1,2 It was first reported in Wuhan, China, at the end of December 200193C5 and found to be highly transmissible (Basic reproduction number ranging from 0.9 to 6.53).4,6 The genome of SARS-CoV-2 is plus (+) sense single-stranded (ss) RNA of size approximately 30 kb that encodes 16 non-structural proteins (nsp1-nsp16), the open reading frames (ORFs) accessory proteins 3a, 6, 7a, 7b, 8, 10. It also encodes four structural proteins viz., the spike protein (S) that forms trimeric structure, matrix/membrane-protein (M), nucleocapsid-protein (N), and an envelope-protein (E) most likely forms ion channel.7C9 The SARS-CoV-2 exudes spherical morphology and unsegmented RNA genome, with 30 poly-A tail and 50 cap-structure.10 Error-prone replication is exhibited Parathyroid Hormone (1-34), bovine by RNA-dependent-RNA polymerase enzyme of RNA viruses which results in Parathyroid Hormone (1-34), bovine an increased mutation rate.11 Though, a high mutation rate (nucleotide-nt substitution per-site/cell infection) is shown by ssRNA viruses, however, in the case of SARS-CoV-2, fixed mutations in the genome have been observed which suggests that SARS-CoV-2 changes slowly (estimated mutation rate/site year = 1.1210?3 nt?1 year?1) as compared to other ssRNA viruses.12,13 Adaptation of SARS-CoV-2 in the population and its global transmission has led to the accumulation of a large number of mutations, especially in spike protein; consequently, various dominant variants and lineages have been formed in year years.14 Lineage switching, generation of SARS-CoV-2 variants, and their continued global spread have aroused serious health concerns.15 The World Health Organization (WHO) has given nomenclature to these variants as variants of interest (VOI) and variants of concern (VOC).16 Major VOCs which had overwhelmed countries around the world encompass; alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B1.617.2).17 A highly transmissible variant of SARS-CoV-2 designated as Omicron was first reported in Botswana (in early November) and in South Africa dated 24-Nov-2021.18 Omicron showed many mutations (n=32), especially in spike protein alone as compared to mutation (n=16) in the tremendously infectious delta variant. The emergence of the Omicron variant (B.1.1.529) led to another fresh wave of Parathyroid Hormone (1-34), bovine the COVID-19 pandemic. This new variant was considered to be the most mutated SARS-CoV-2 variant.18,19 VOC are lethal variants capable of bringing about detrimental alterations in COVID-19 epidemiological parameters. A few variants, especially VOCs have raised grave epidemiological concern.20 Compared to the early-mutants or wild-type (WT) strains, these newly emerged SARS-CoV-2 variants have triggered successive COVID-19 waves with varying epidemiological features.21,22 Wild-type (WT) strain was potentially fatal among aged people with comorbid conditions; however, recent pre-clinical, clinical, and epidemiological data suggest that a vast number of emerged variants, VOCs in particular, are capable of breaching epidemiological barriers and have the potential to cause considerable fatality across the various demographic groups in different geographical locations including Al-Baha, Kingdom of Saudi Arabia.21C24 The evolution of VOCs impacts increased human-to-human transmissibility, virulence, pathogenesis, clinical manifestations, and debilitated effectiveness of the public health-safety and social measures.17 It could also influence diagnostic and therapeutic countermeasures at a greater length that compels the viral evolution research group to focus on SARS-CoV-2 variants, phenotypic characteristics, and their significant impacts on TPO various countermeasures. The latest recovered Omicron.