deLemus

Summary

The outbreak of COVID-19 caused by SARS-CoV-2 has become a global health crisis. The RNA genome of the virus allows rapid mutation and the emergence of new variants of concern (VOCs), improving its fitness. The deLeMus website provides information about the key mutations of different variants that have surged since the outbreak. One mutation captured is N440K, which is in the RBD of the spike protein that is present in BA.1, and it caused resistance to imdevimab [https://doi.org/10.1038/s41579-022-00809-7]. From the mutational information, we can investigate the patterns of mutation of the virus, allowing further research on their functions and possibly prediction of new variants in the future.

Since the outbreak of COVID-19, there have been new variants emerging. Omicron, the latest 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, which is 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, G257S, 3 mutations in the N-terminal domain (NTD), and N460K, a mutation in RBD, which are 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.

In addition to that, deLemus can reveal emerging sites that could potentially show up in future variants. By tracking and evaluating the mutation activity in the virus from the beginning of the pandemic, we have identified sites in different domains of the spike protein.  For the Receptor Binding Domain (RBM), we have outlined potential sites as shown in the figure below.  Most of the mutation sites reported by deLemus have been found in different Omicron lineages, and thus it is possible that the remaining sites marked as red circles may be established in variants in the near future. In fact, one of the outlined mutations S494P has been shown by studies to disrupt the binding of antibodies and escape vaccines, possessing similar properties to previously reported mutations in Omicron such as N440K and G446S.

Leading Mutation Map

TEMP

Variant Distribution

TEMP