Mutational Analysis of Circulating Omicron SARS-CoV-2 Lineages in the Al-Baha Region of Saudi Arabia

PURPOSE: Omicron (B.1.1.529) is one of the highly mutated variants of concern of SARS-CoV-2. Lineages of Omicron bear a remarkable degree of mutations leading to enhanced pathogenicity and upward transmission trajectory. Mutating Omicron lineages may trigger a fresh COVID-19 wave at any time in any region. We aimed at the whole-genome sequencing of SARS-CoV-2 to determine variants/subvariants and significant mutations which can foster virus evolution, monitoring of disease spread, and outbreak management. METHODS: We used Illumina-NovaSeq 6000 for SARS-CoV-2 genome sequencing, MEGA 10.2 and nextstrain tools for phylogeny; CD-HIT program (version 4.8.1) and MUSCLE program for clustering and alignment. At the same time, UCSF Chimera was employed for protein visualization. RESULTS: Predominant Omicron pango lineages in Al-Baha were BA.5.2/B22 (n=4, 57%), and other lineages were BA.2.12/21L (n=1, 14.28%), BV.1/22B (n=1, 14.28%) and BA.5.2.18/22B (n=1, 14.28%). 22B nextstrain clade was predominant, while only one lineage showed 21L. BA.5.2/22B, BA.5.2/22B harbored a maximum of n=24 mutations in the spike region. Twelve crucial RBD mutations: D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, and Y505H were identified except the lineage BA.5.2/22B in which F486V mutation was not observed. Critical deletions S106 in membrane protein NSP6, E31in nucleocapsid, and L24 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.