Time Course
Previously Confirmed Mutations
In the last 6 months, 3 omicron sublineages have been announced as Variant of Interest (VoI), which are BA.2.75, BQ.1, and XBB. These variants bring new mutable sites that are very important for the virus to improve its fitness.
N460K
N460K mutation is first reported in B.2.75, which became prevalent by July 2022. The mutation from Asparagine(N) to Arginine(R) at site 460 can increase the hACE2-binding affinity with the background of BA.2 mutation in the deep mutational study(DMS). Moreover, this mutation also grants immune evasive capability over monoclonal antibodies(mAbs). Not only in BA.2.75, but this mutation also shows up in the subsequent VoIs (BQ.1 and XBB). deLemus already outlined this mutation by February 2022, much earlier before it became prevalent.
F486V/S, K444T
F486V mutation previously showed up in BA.4&5 lineage. This mutation also shows up in the BQ.1 lineage and exhibits polymorphism in the XBB lineage, with the mutation from Phenylalanine to Serin (F486S). This mutation facilitates the escape from class I and II mAbs and the DMS study also reveals the same immune evasion capability over COV2-2832 mAb. deLemus outlines the mutation activity in this site by March 2022. The mutation K444T is reported in BQ.1 as well. This mutation has been reported to abolish the 2X324-neutralizing activity with various amino acids. deLemus also outlined the mutation in this site by the end of 2021.
R346T, R368I, and V445P
These three mutations have never been reported in the previous variants and currently show up in the XBB variant. The mutation at site 346 was previously reported in the lambda variant, but with the amino acid Lysin(R346K) instead of Threonine(R346T) as in XBB. deLemus detected the mutation activity in this site by the end of 2021, which persistently exhibits high signal ever since. For site V445, deLemus also has detected the mutation signal in this site since April 2022. The DMS study reported an escape capability of this site over mAbs COV2-2449.