deLemus

RBD Outlined Mutations Update (30/12/2022)

Summary

The deLemus website provides information about the leading mutations of in spikes glycoprotein of SARS-CoV-2. From the leading mutations, we can investigate the mutation patterns of the virus, allowing further research on their functions and possibly prediction of new variants in the future. Omicron, the latest SARS-CoV-2 lineage designated as a VOC by the WHO after being reported in South Africa in November 2021, has various subvariants, including BA.1 (the first subvariant of omicron), BA.2, BA.4, and BA.5. Omicron was spreading very quickly to many countries after its first report. Soon after the discovery of BA.1, BA.2 was detected and spread across the globe. In April 2022, BA.4 and BA.5 were monitored by the WHO after being found in multiple countries, and they showed a significant increase in growth advantage when compared to BA.2. These two variants became dominant in the UK, the US, and Germany in June 2022. In the meantime, BA.2.12.1 and BA.2.75 were also spreading in the US and India respectively in May 2022. In August 2022, XBB, a recombinant of BA.2.10.1 and BA.2.75, was found to have a small outbreak in various countries such as Singapore and Bangladesh. After that, in October 2022, BQ.1, which is a subvariant of BA.5 prevalent in France, was found.

The omicron variant is notorious for having a large number of mutations, some of which are known to be involved in escaping various antibodies. The deLemus website has captured many of these mutations, one of which is F486V in BA.4 and BA.5. It has been reported in some research showing that this loss of phenylalanine in the RBD of the spike protein is in a lot of binding sites of monoclonal antibodies (mAbs). S704L, a reported novel mutation in BA.2.12.1 in the post-RBD region of the spike, has also been captured by deLemus. The captured BA.2.75 mutations include K147E, I210V, and G257S, 3 mutations in the N-terminal domain (NTD), and N460K, an RBD mutation which is all reported. For BQ.1, deLemus captured a reported RBD mutation K444T. Two reported mutations, H146Q (NTD) and V445P (RBD), are detected by deLemus for XBB.

Newly Reported 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 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 evasive potential 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 abrogate 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, it shows 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.

Outlined Mutations

In addition, deLemus can reveal emerging sites that could potentially appear in future variants. By tracking and evaluating the mutation activity in the virus from the beginning of the pandemic, we have captured potential sites in different domains of the spike protein, especially RBD.

K356T

Among all the detected mutations in spikes protein, this site is worthy to be monitored due to its persistent signal since April 2022. The mutation from Lysin(K) to Threonine(T) at site 356 enables N-X-T sequon, which is crucial for glycosylation, a defense mechanism for the virus to hide from immune surveillance, e.g., antibodies. Moreover, the emerging variant provided by GISAID also reveals that the R356T mutation shows up in the top 5 accelerating variants, the BN.1.4 variant.

Monthly Leading Sites

TEMP

Leading Mutation Map

TEMP