deLemus

Update (30/12/2022)

Summary

The deLemus website provides information about the leading mutations 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.

Confirmed Mutations

As explained above, deLemus can outline potential mutations in the coming time. In this section, we provide the outlined mutations that are currently confirmed in the emerging variant (EV).

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.

F486P/I

The next mutation is F486P/I. Mutation from Phenylalanine (F) to Proline (P) at site 486 shows up in the recent accelerated variant, XBB.1.5, which is currently showing substantial growth in the US. This mutation renders higher hACE2-binding affinity compared to its ancestor (XBB.1), that is likely responsible for its high growth. . We also noticed another leading mutation on the same site, F486I, which could be a dangerous mutation in the coming time.

References