Evolution of the “omicron”: from mouse to cat, from cat to mouse, from mouse to human

(ORDO NEWS) — The scientists investigated the BA.1 and BA.2 omicron subvariants and tested their ability to bind to the human, mouse and cat ACE2 membrane protein.

In the end, they concluded that the mouse was the main host for the evolution of the “omicron”, which passed through the cat, returned to the mouse, and then moved on to humans.

The World Health Organization announced on March 22 that the BA.2 subvariant of the omicron strain has become the dominant form of SARS-CoV-2, the virus that causes Covid-19, worldwide. BA.2 shares many genetic similarities with its close relative BA.1, which has led to a global spike in the incidence in recent months.

But BA.2 is 30-50 percent more contagious than BA.1. It quickly spread around the world and became the dominant variant due to its higher infectivity.

The spike protein is the S protein that makes up the shell of the coronavirus and with which it clings to human cells.

Chinese researchers biochemically analyzed the binding affinity of the BA.2 spike protein to the human ACE2 enzyme: their work showed an affinity approximately two times higher than that of BA.1 and 11 times higher than that of the WT strain (wild type).

The interaction of the spike protein with ACE2 is the first step in the binding of the virus to the host receptor, which is critical for pathogen entry and subsequent infections. Thus, the higher binding capacity of the BA.2 spike protein probably determines its special transmissibility.

In addition, the results of the study helped to identify a possible original host for BA.1 and BA.2. Omicron has been reported to have evolved independently of all other coronavirus strains and its origin remains a mystery.

Investigating the origins of BA.1 and BA.2 is critical to the effective control and prevention of Covid-19 in the human population.

Mutation profiling analysis suggests that the “omicron” variants may have evolved through mouse as a host. In a new study, biochemical data confirmed that the BA.1 and BA.2 spike proteins are able to bind with high affinity to mouse and cat ACE2.

At the same time, the spike protein of the WT strain binds well to cat ACE2, but does not bind to mouse ACE2. This indicates a high susceptibility of mice and cats to BA.1 and BA.2.

“We identified spike structures from both BA.1 and BA.2 in complex with the mouse ACE2 protein and identified three residual mutations that are required for binding to the mouse ACE2 protein, indicating their importance in infections.

Surprisingly, two of the three required mutations were found in mouse-adapted SARS-CoV-2 and have not been identified in any SARS-CoV-2 variants from other animals since then,” said one of the authors of the study.

Based on data from their work, combined with previous work, the scientists hypothesized that the mouse is likely the key animal host for the evolution of the omicron variants.

“Taken together, our data reveal a structural and biochemical understanding of the increased transmissibility and binding of BA.2 antibodies, as well as a possible evolutionary path for omicron variants. According to our data, they went from a person to a cat, then to a mouse, and then back to a person.

Although such an evolutionary path is highly speculative, the ability of omicron variants to infect and spread among mice and possibly other animals could have important implications for the development of control strategies in the fight against coronavirus infection, ”concluded the authors of the study.

The Omicron strain turned out to be so different from the earlier ones that both the vaccines and the immunity of those who have been ill are only limitedly effective against it.

If a similar path of mutations – through animals living next to humans – repeats, we may expect another strain that can bypass past variants of anti-coronavirus immunity.

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