McGill University Researcher Detects Two New Omicron BA.1.1 Subvariants BA.1.1I and BA.1.1H And A New Delta Subvariant D1K In New Zealand
Source: Medical News - BA.1.1 Subvariants BA.1.1I amd BA.1.1H Mar 16, 2022 2 years, 9 months, 1 week, 1 day, 16 hours, 38 minutes ago
A researcher from McGill University-Canada, Dr Xiang-Jiao Yang has detected two new Omicron BA.1.1 subvariants ie BA.1.1I and BA.1.1H and a new delta subvariant in New Zealand with the new BA.1.1 subvariants possibly driving the new COVId-19 surges there.
The Omicron variant after initial identification in November 2021, has yielded three different subvariants, BA.1, BA.2 and BA.3.
The BA.1 is dominant around the world although BA.2 is gradually taking over this role.
The BA.1 variant has acquired spike R346K and yielded a sub-lineage known as BA.1.1.
Dr Xiang analyzed new SARSCOV-2 genomes identified in Oceania and Asia, where there are many ongoing pandemic hotspots.
Surprising, the analysis revealed that together with BA.2, two different BA.1.1 strains are dominant in New Zealand.
Each of these new BA.1.1 subvariants 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.
Detailed 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.
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2022.03.15.484404v1
From the GISAID database,the first Omicron BA.1 case was identified on December 07, 2021 in New Zealand.
https://www.gisaid.org/
The first BA.1.1 case was reported one week later, whereas the first BA.2 case (EPI_ISL_8648633) was identified on January 01, 2022. But the new pandemic wave only started to surge at the beginning of February 2022.
https://ourworldindata.org/coronavirus
Interestingly, this 2-month delay from the initial omicron case at the beginning of December 2021 raises the intriguing possibility that omicron variant gains additional mutations during the period.
In order to investigate this possibility, Dr Xiang analyzed 1,109 omicron genomes identified in the country after February 01, 2022. The genomes were downloaded from the GISAID database on March 11, 2022 for mutation profiling via Coronapp, a web-based COVID-19 genome annotator.
It was found that many genomes carry 65-70 mutations per genome. This is close to the average mutation load of the omicron genomes initially identified in South Africa. Due to incomplete sequence coverage, some omicron genomes from New Zealand apparently carry fewer than 65 mutations per genome.
Dr Xiang told Thailand
Medical News
;, “Both the B.1.1 and BA.2 subvariants are dominant, with only a few genomes encoding BA.1 itself. Thus, B.1.1 and BA.2, but not BA.1 itself, are the main culprits for the ongoing wave of COVID-19 cases in New Zealand.”
Although no new substitutions are present in the genes of spike and nucleocapsid proteins, one new NSP3 substitution, T1368I, was identified.
Further inspection of all other genes uncovered two more new substitutions, L133F of NSP10 and R289H of NSP14.
All these three new substitutions are in BA.1.1 genomes, so BA.2 genomes have not gained any dominant new mutations. While L133F of NSP10 is present in over 700 B.1.1 genomes out of the 1,109 omicron genomes analyzed, T1368I of NSP3 and R289H of NSP14 are mutually exclusive, present in two different portions of BA.1.1 genomes analyzed.
Hence, there are two new BA.1.1 derivatives encoding L133F of NSP10 along with T1368I of NSP3 or R289H of NSP14.
For convenience, these two strains are referred to BA.1.1I and BA.1.1H, where the letters I and H denote I1368 of NSP3 and H289H of NSP14, respectively.
As for the potential mechanistic impact of the new substitutions, T1368I of NSP3 is located close to its first transmembrane domain, so the precise impact is not obvious.
L133 of NSP10 is located within an unstructured C-terminal tail close to D131, so the impact remains unclear.
However, R289 of NSP14 is away from the binding sites for NSP10 and RNA, importantly, this residue is a part of a key motif forming the binding pocket for Sadenosyl methionine, a cofactor required for the guanine-N7 methyltransferase activity. This motif contains 289-RDVW-292, where the last three residues are almost invariant. Consistent with this, replacement of W292 is known to diminish the guanine-N7 methyltransferase activity of NSP14.
The first BA.1.1 genome encoding L133F of NSP10 was identified in New Zealand on December 31, 2021 (EPI_ISL_8648550). Two or three days before that, two such genomes were identified in the United Kingdom (EPI_ISL_8440340) and the United States (EPI_ISL_8623811). The first BA.1.1I and BA.1.1H genomes (EPI_ISL_9209954 and EPI_ISL_9210460, respectively) were only identified about three weeks later.
Both have subsequently contributed significantly to the surge of COVID-19 cases starting at the beginning of February 2022. These results also suggest the potential evolutionary trajectory of these two BA.1.1 derivatives. As described above, the first BA.2 genome was identified on January 01, which is about three weeks before the first BA.1.1I and BA.1.1H genomes were recovered.
However, among the 1,109 omicron genomes analyzed, there are fewer BA.2 genomes than the combined B.1.1I and B.1.1H genomes, suggesting that BA.2 is less potent in driving the pandemic in New Zealand.
In terms of other countries, only one BA.1.1I case and two BA.1.1H cases have been identified in Australia.
Dr Xiang said that it will be important to track how these two strains will fare there.
Also, a new Delta subvariant was discovered in New Zealand that carries over ten new mutations
Detailed analysis of newly identified SARS-COV-2 genomes identified in New Zealand also uncovered 116 genomes encoding a new Delta variant.
The genomes harbor d1 subvariant-specific substitutions, such as A488S, P1228L and P1469S of NSP3, as well as G215C of nucleocapsid.
This new Delta subvariant was first identified in the country on Dec 28, 2021 (EPI_ISL_8825465). The subvariant possess over ten new substitutions, including N481K and R765H of spike protein, N140S of nucleocapsid protein; G283S of NSP3; T204I of NSP4; P43L and L508F of NSP14; and V71I, F101LRQ* and other deletions of NSP7a.
The abundance of related precursor d1 genomes with one or some of these mutations suggests a gradual evolutionary trajectory.
Simply for convenience, this subvariant is referred to as d1K, where the letter K refers to K481 of spike protein.
However, despite its over ten more mutations than a typical Delta subvariant, d1K only plays a very minor role in driving the pandemic in New Zealand, mainly due to predominant omicron BA.1.1 and BA.2 subvariants.
Related to this, the d1K genomes carry an average of 50-51 mutations per genome. Compared to other known with Delta subvariants, this is one of the most advanced Delta subvariant in terms of its mutation load.
But this is still far below the mutation load of close to 70 mutations per omicron genome. Compared to d1K, such a high mutation load in omicron variant raises an intriguing but unaddressed question as to the origin of this surprising variant.
The study team warns that the new mutations may enhance the potency of these emerging subvariants.
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