Omicron variant of SARS-COV-2 gains new mutations in New Zealand and Hong Kong (preprint)

ABSTRACT

SARS-COV-2 evolution is a key factor that drives the pandemic. As the previous four variants of concern, omicron variant arose from complete obscurity and have rapidly become the prominent pandemic driver around the world. After initial identification in November 2021, this variant has yielded three different subvariants, BA.1, BA.2 and BA.3. Among them, BA.1 is dominant around the world although BA.2 is gradually taking over this role. BA.1 has acquired spike R346K and yielded a sub-lineage known as BA.1.1. An important question is how these variants continue their evolution. To address this question, I analyzed new SARS-COV-2 genomes identified in Oceania and Asia, where there are many ongoing pandemic hotspots. This analysis revealed that together with BA.2, two different BA.1.1 strains are dominant in New Zealand. Each of them carries two new substitutions, with L133F of NSP10 as the common one. This residue is located at an unstructured C-terminal tail, so the impact of L133F is not obvious. The other new substitutions are T1368I of NSP3 and R289H of NSP14. While T1368I of NSP3 is located close to its first transmembrane domain, R289H of NSP14 is right at a key motif of the binding pocket for S-adenosyl methionine, a cofactor required for the guanine-N7 methyltransferase activity. Analysis of SARS-COV-2 genomes from New Zealand also identified a delta subvariant with over ten new mutations (including spike N481K and R765H), but the subvariant is still negligible in driving the pandemic. Analysis of SARS-COV-2 genomes from Hong Kong uncovered a predominant BA.2 subvariant with three new substitutions I1221T of spike protein (located at the transmembrane domain), T725I of NSP3 (within the C-terminal third of a SARS-unique domain) and T145I of NSP8 (at a surface area away from the site for interaction with NSP7 and NSP12). By contrast, no dominant mutations are obvious in omicron genomes from Australia, Indonesia, Singapore, Malaysia, Thailand, Japan and South Korea, suggesting that emergence of the dominant omicron subvariants in New Zealand and Hong Kong is of random nature. These findings partly explain the current situation in these two pandemic hotspots and reiterate the importance to continue tracking SARS-COV-2 evolution.