New coronavirus mutations largely saturated? Experts explain it this way

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Recently, some epidemiologists have commented that the mutation of the new coronavirus is basically saturated. Is there really no more mutation in neo-coronaviruses?

At previous academic meetings, several experts have discussed the question of where neo-coronavirus mutations will go.

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Zhang Wenhong, director of the Department of Infection at Huashan Hospital of Fudan University, emphasized the pressure of the body’s immunity against viral mutations. He said that viruses have always had the “urge” to mutate, but that active immunity in humans, or immunity from infection and repeated infections, can limit the direction of neo-coronavirus mutation.

Gao Fu, a member of the Chinese Academy of Sciences, looked at virus mutation in the broad context of the entire natural world, saying that the host range of the new coronavirus is very wide, from tigers and lions to mice and rabbits, and is still expanding further, and that the new coronavirus may pose a greater challenge cannot be ignored.

Whether it is the constraints of human immunity on the direction of virus mutation or the possibility of “repeated cross-jumps” between species, both experts’ views suggest that there are many factors to consider in predicting the mutation of a new coronavirus.

So, will the new coronavirus mutation occur “saturation”? Science and Technology Daily reporter interviewed virologists online.

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The average annual mutation of 24 loci

“The mutation rate of the new coronavirus is an average of 24 loci per year.” Virology experts, Beijing University of Chemical Technology College of Life Sciences and Technology Dean Tong Yigang told reporters that this means that three years have passed, the existing sequence of the new coronavirus compared with the sequence of the original strain, the average number of mutated bases will be about 70-80.

Why does the neo-coronavirus mutate at a relatively steady rate?

“Neo-coronaviruses have error correction mechanisms, and mismatches (which do not follow the A-U, C-G principle) inevitably occur during viral replication, such as the lack of error correction mechanisms in influenza viruses and AIDS viruses, and mutations occur after mismatches.” Tong Yigang said, but the new coronavirus is different, after the mismatch will have its own error correction mechanism to correct some of the mismatched bases.

Because of the error correction mechanism, the neo-coronavirus is like a modern factory with an online quality control system, and the probability of error during replication is relatively small.

“The full-length genome of neo-coronavirus has more than 30,000 bases, and even if we focus only on the RBD region of the S protein, there are still several hundred bases, and mathematically speaking, neo-coronavirus mutation is still far from saturation.” Tong Yigang said.

In addition, as RNA viruses, neo-coronaviruses have different modes of mutation, including progressive mutation (base mutation), and jump mutation (gene recombination, for example, XBB is a recombinant of BA.2.10.1 and BA.2.75 sublineages). These also make it difficult to reach “saturation” of viral mutations.

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Current viral mutations focus on immune escape and future drug resistance

Most of the research on neocoronavirus mutations is currently focused on a few hundred bases in the RBD region of the S protein. What effect changes in the other regions of more than 20,000 bases have on the virus has not been studied in depth.

Currently, vaccination has helped to establish an immune barrier for the whole population, making the new coronavirus continuously change the RBD region of the S protein to achieve immune escape because it has to respond to the immune pressure of the human host.

In future battles with the virus, humans still need to create a more demanding environment through research and innovation to sharpen the “claws” of the new coronavirus. Tong Yigang said, for example, in order to prevent the future of the new coronavirus in drug resistance, environmental resistance and other aspects of the mutation of other sites, drug development should have a broader perspective, should encourage the development of multiple mechanisms of action of the new coronavirus drugs, in order to avoid the generation of drug resistance to the virus brought about by a single drug target.

“Human research on neo-crown virus is not yet said to be thorough enough.” Tong Yigang made an image analogy, the limit of 100 meters running time of human is within 10 seconds, cheetah’s is more than 3 seconds, still need more scientific research to limit the pathogenic potential of neo-coronavirus.

Herd immunity exerts enormous pressure on the evolution of the new coronavirus

Zhang Wenhong has confessed, “Although the mutation of the virus is directionless, the evolution of the virus is regular and directional. The low virulence of the current virus makes the spread of the virus impossible for us to track and give the first warning, which facilitates its evolution.”

The current faster spreading and more clinically insidious Omicron has the advantage of survival in the new coronavirus. Based on this, Wenhong Zhang believes that jumping out of the Omicron strain family to give birth to another faster-spreading strain is now difficult.

“With the continued international use of vaccines against variant strains of Omicron, the virus needs to spread stealthily, so the less virulent the strain, the faster it will spread.” Wenhong Zhang said.

Over the past three years, the evolutionary trajectory of the new coronavirus has invariably borne traces of immune interactions with the host. The high rate of vaccination in the population and the organism’s immunity from reinfection will always guide the evolutionary direction of the new coronavirus, which several experts believe will eventually become like the common human coronavirus HCoV-OC43, which no longer produces severe symptoms.