Wednesday, January 19

Omicron may not be the final variant …


It is controversial if viruses are alive, but, like all living things, they evolve. This fact has become very clear during the pandemic, since new variants of concern they have cropped up every few months.

Some of these variants have spread better from person to person, eventually becoming dominant as they overtake the slower versions of SARS-CoV-2, the virus that causes COVID-19. This improved spreading ability has been attributed to mutations in the spike protein, the mushroom-shaped projections on the surface of the virus, which allow it to bind more strongly to ACE2 receptors. ACE2s are receptors on the surface of our cells, such as those that line our airways, to which the virus attaches itself to enter and begin to replicate.

These mutations allowed the alpha variant, and later the delta variant, to become globally dominant. And scientists hope the same will happen with omicron.

However, the virus cannot improve indefinitely. The laws of biochemistry mean that the virus will eventually develop a spike protein that binds to ACE2 as tightly as possible. At that point, the ability of SARS-CoV-2 to spread between people will not be limited by how well the virus attaches itself to the outside of cells. Other factors will limit the spread of the virus, such as how quickly the genome can replicate, how quickly the virus can enter the cell through the TMPRSS2 protein, and how much virus an infected human can kill. . In principle, all of these should eventually evolve to peak performance.

Has Omicron reached this peak? There is no good reason to suppose that it is. So-called “gain-of-function” studies, which look at the mutations that SARS-CoV-2 needs to spread more efficiently, have identified a lot of mutations They enhance the spike protein’s ability to bind to human cells that omicron does not have. In addition to this, improvements could be made to other aspects of the virus life cycle, such as genome replication, as I mentioned earlier.

But suppose for a second that omicron is the variant with maximized propagation capacity. Perhaps omicron will not improve because it is limited by genetic probability. In the same way that zebras have not developed eyes on the back of the head to avoid predators, it is plausible that SARS-CoV-2 cannot detect the mutations necessary to reach a theoretical maximum, since those mutations must occur all at once, and is highly unlikely to arise. Even in a scenario where omicron is the best variant to spread between humans, new variants will emerge to manage the human immune system.

After infection with any virus, the immune system adapts by producing antibodies that attach to the virus to neutralize it and killer T cells that destroy infected cells. Antibodies are protein fragments that adhere to the specific molecular shape of the virus, and killer T cells also recognize infected cells through the molecular shape. Therefore, SARS-CoV-2 can evade the immune system by mutating enough that its molecular shape changes beyond recognition by the immune system.

This is why omicron is apparently so successful at infecting people with prior immunity, either from vaccines or infections with other variants, the mutations that allow the spike to bind to ACE2 more strongly as well. reduce the capacity of antibodies to bind to the virus and neutralize it. From Pfizer the data suggest that T cells should respond similarly to omicron than to earlier variants, which aligns with the observation that omicron has a lower mortality rate in South Africa, where most people have immunity.

It is important to humanity that past exposure still appears to protect against serious illness and death, leaving us with a “compromise” in which the virus can replicate and re-infect itself, but we do not get as seriously ill as the first time.

Probable future

Herein lies the most likely future of this virus. Even if he behaves like a professional gamer and eventually maxes out all of his stats, there is no reason to think that he will not be controlled and eliminated by the immune system. Mutations that enhance its ability to spread do not increase kills much. This maxed-out virus would simply mutate randomly, changing enough over time to become unrecognizable to the immune system’s adapted defenses, allowing waves of reinfection.

We may have COVID season every winter in the same way that we have flu season now. Influenza viruses can also have a similar pattern of mutation over time, known as “antigenic drift”, Which causes reinfections. Each year’s new flu viruses are not necessarily better than last year’s, just different enough. Perhaps the best evidence of this eventuality for SARS-CoV-2 is that 229E, a coronavirus that causes the common cold, already does this.

So, Omicron won’t be the final variant, but it may be the final variant of concern. If we are lucky and the course of this pandemic is difficult to predict, SARS-CoV-2 is likely to become an endemic virus that slowly mutates over time.

The illness is most likely mild, as past exposure creates immunity that reduces the likelihood of hospitalization and death. Most people will be infected the first time as children, which could happen before or after a vaccination, and subsequent reinfections will hardly be noticeable. Only a small group of scientists will track the genetic changes of SARS-CoV-2 over time, and the variants of concern will become a thing of the past, at least until the next virus jumps the species barrier.The conversation

Ben krishna, Postdoctoral Researcher, Immunology and Virology, University of Cambridge

This article is republished from The conversation under a Creative Commons license. Read the Original article.


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