BA.2.75 aka Centaurus is spreading quickly, mostly in India right now, but has been found in at least 10 other countries, including the US. Right now, the most dominant strain is BA.5. But lets rewind a little bit to understand these subvariants of omicron.
Omicron BA.1 variant emerged this past winter with major genetic differences. BA.1 was quickly followed by BA.2. BA.1 and BA.2 comprised most of the cases this past winter and early spring, with around 1 million cases per day in the US. BA.4 and BA.5, which are very similar, derive from BA.2, as does BA.2.75, although independently.

There is no relation between Omicron BA.1 and the other major variants, meaning no relation to Alpha, Beta, Gamma, Delta. BA.4 and BA.5 are more than capable of reinfected those with previous covid infections, including those who’ve had omicron. That’s regardless of vaccination status as well.

Just like those infected with omicron BA.1 were susceptible to BA.2, and so on. This report indicated that BA.5 was about15-fold more resistant to the monoclonal antibody treatent Evusheld and Sotrovimab compared with previous variants.

This resistance, in addition to new mutations, is likely related to sensitivity to a membrane protease, TMPRSS2, that is associated with cell membrane infectivity.

BA.5 has a greater sensitivity to TMPRSS2 inhibitor Nafamostat, meaning that BA.5 could be more similar to the Delta variant of 2021. Especially when you consider that BA5 is getting into the lungs on a more frequent basis, compared to omicron.

But what about the newest subvariant of omicron, BA.2.75? On July 7th the WHO classified it as a variant-of-concern, and its being monitored closely. It has a specific group of mutations in its spike protein, in addition to those found in BA.2, BA.4, BA.5, and other mutations outside the Spike protein?

The Spike is the most heavily mutated protein in the Omicron family.

There are 36 mutations in the spike protein of BA.2.75.

To put that in perspective, some variants like alpha didn’t even have that any in its entire genome. The unique mutations of the BA.2.75 Spike protein are located in 2 regions: the RBDomains, and the N-terminal.

The receptor-binding domains (RBD) are the typical targets for neutralizing antibodies. Neutralizing antibodes that come from either vaccine immunity, immunity from previous infection, or in the form of monoclonal antibody treatment.

So when you have mutations in this location, that means there is a higher probability that those antibodies will be useless.

In this study, they generated pseudoviruses that harbored the spike proteins of BA.2.75, BA.4/5 and BA.2 and evaluated the effectiveness of ten different monoclonal antibodies treatments on them.

In this pre-print study, but based on these preliminary findings, the authors concluded that 3 of the monoclonal antibody treatments (regdanvimab, sotrovimab, and tixagevimab) unfortunately did not exhibit antiviral effects against BA.2 and BA.4/5. But the good news is that it did so against BA.2.75, which suggests that these antibodies can be used for the treatment and prevention of BA.2.75 infection.

But the spike protein mutations, its not just about escaping antibodies. Its also allows it to be more transmissible, when those mutations promote better binding to the ACE2 protein on our cells.

And because of this, and because of the antibody escape, it continues to be a cat and mouse game between our immune system, and new covid variants that keep mutating, that keep evolving.

And that’s why it’s a continuous back and forth of adapting new vaccines that fight these new variants, like the new bivalent vaccine that is expected to battle BA.4, BA.5, and BA.2.75, likely being made available in the fall or winter. In addition to BA.2.75, recent reports from India suggest that there are associated lineages BA.2.74 and BA.2.76 that are also circulating right now. So there’s more to come with these variants, so we’ll see.
But the bottom line? Covid isn’t going anywhere. And with BA4, BA5, and now BA2.75, circulating in high numbers, the risk of getting infected, or re-infected, remains high.

#covid #omicron #omicronvariant

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