Quick Note: Subvariants of the SARS-CoV-2 Omicron Variant

You may have gotten word of a new SARS-CoV-2 “subvariant” to Omicron. In fact, there are a currently two, called BA.1 and BA.2. (Yes, the terminology and nomenclature are really confusing…)

I have taken a quick look at the predicted structures for the receptor-binding domains (RBDs) of each subvariant. Want to know my thoughts?

Compared to the Omicron variant from November 2021, BA.1 contains no additional mutations in the RBD (when compared to the OG Wuhan isolate from 2019). BA.2, on the other hand, contains 4 new mutations (L371F, T376A, D405N, R408S) and has reverted (reverse mutated?) back to what we saw in the original Wuhan isolate in 2 positions (S446G, S496G).

AlphaFold2-predicted BA.2 structure (in blue) compared to the original Omicron structure (in green, PDB: 7T9J). Mutations from Omicron to BA.2 are in red and reverse mutations back to Wuhan are in yellow. BA.1’s sequence matches Omicron’s, so no structure to show.

In terms of vaccine efficacy and reinfection likelihood, if you’ve already had Omicron and/or have been vaccinated and boosted, I don’t see any huge cause for alarm. For many neutralizing antibodies that dock to the “up” position (top) of the RBD, the two mutations that occur in this area (in yellow) are more similar to the older version of the virus (which the vaccines are based on). So, this may be a good thing in terms of vaccine efficacy and existing antibody binding.

What we may be seeing here is convergent evolution where, instead of Omicron actually mutating into BA.1 and BA.2, BA.1 and BA.2 may have mutated independently but in a similar way. We see this happen when there are pressures on an organism to survive. One other option is genetic recombination where a person was infected with two variants at the same time and, during the viral replication process in the body, the sequence information got mixed together to create a hybrid variant. (Hard to prove, but possible.)

When this virus’ goal is to continue to infect and reproduce while also evading antibodies, it is advantageous for this virus to mutate in this domain.

In short, these “subvariants” are really just one of many sets of mutations that we’ll see in Omicron-like variants. As the virus continues to mutate, we may see variants that evade existing vaccines or ones that are easier to spread. BA.2, though, seems to be somewhere between an older variant and Omicron, so not really a huge cause for concern (in terms of vaccines and re-infection risk).

If you’re interested in looking at the BA.1 and BA.2 sequences for yourself, you can find them here: https://github.com/colbyford/SARS-CoV-2_B.1.1.529_Spike-RBD_Predictions/tree/main/subvariants

Stay Curious.



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Colby T. Ford, PhD

Colby T. Ford, PhD

Cloud genomics and AI guy and aspiring polymath. I am a recovering academic from machine learning and bioinformatics and I sometimes write things here.