Three questions about "Omi Keron": Is there a "super virus" if there are too many mutations?

　　◎Reporter Zhang Jiaxing

　　With more than 30 mutated amino acids in key proteins, the new coronavirus mutant strain "Omi Keron" was quickly designated as a "VOC" (VOC) by the WHO.

　　The number of site mutations in the new crown virus strain "Omi Keron" has "surged". Where did the super-multiple mutations come from?

Will changes become "super mutations"?

Are vaccines and drugs still effective?

　　With three questions about "Omi Keron", Science and Technology Daily exclusively interviewed Tong Yigang, the dean of the School of Life Sciences and Technology of Beijing University of Chemical Technology, and the Chinese leader of the Animal and Environment Group of the China-WHO Covid-19 Joint Research Expert Team.

　　One question: Where do so many mutations come from?

　　"The mutation of the virus has a certain frequency and speed." Tong Yigang explained that compared with the volatile influenza virus, the new coronavirus has a slightly slower frequency and speed because of the "error correction" mechanism.

　　What is the "error correction" mechanism?

That is, when the virus is multiplying, it will match one by one according to the RNA strands of the "parental generation". If the "match" is wrong, it will be discovered by the "error correction" mechanism: the copy is wrong, rewrite!

The sequence of the next-generation virus generated in this way will be roughly the same as that of the previous generation, without so many errors.

　　"If the protein related to the replication function and correction function of the new coronavirus is changed, then its error correction mechanism is weakened, which may lead to more mutations." Tong Yigang speculated that if the "Omi Keron" mutant strain is true It is the accelerated mutation, the virus replicase RdRp (RNA-dependent RNA polymerase) or the replication correction protein nsp14 may have some changes.

　　"Whether the core mechanism of the new coronavirus replication has changed requires further verification." Tong Yigang said, if the "Omi Keron" strain mutates during the later period of transmission, and people see more mutations, then It shows that the replication mechanism has indeed changed.

　　Tong Yigang agreed with the judgment that some foreign experts speculated that "Omi Keron" evolved from the body of AIDS patients.

He explained that immunodeficiency patients have weak ability to suppress and select the virus, and the infection may persist. Various mutations produced by the virus may be retained, and the more and more they accumulate, the mutant strain containing a large number of mutations will eventually be formed.

　　Second question: Will too many mutations make the virus worse?

　　Since a large number of mutations are caused by the accumulation of mismatches and small selection pressure, it is not difficult to understand that the super-many mutations of "Omi Keron" are not all critical.

　　"The variation of some sites is random and does not make much sense. The mutations of some sites may make it less pathogenic, and some may increase its pathogenicity." Tong Yigang explained that all these require follow-up clinical practice. To prove that the pathogenicity of a virus strain can also be verified at the cell, animal, etc. level, but there is no relevant scientific research yet.

　　"At present, the infection ability is indeed enhanced." Tong Yigang said. For example, the N501Y mutation, which is more concerned by the academic community, will make the virus S protein and the human cell ACE II receptor stronger, like the tooth pattern of the key is more in line with the keyhole.

　　A reporter from Science and Technology Daily found that the mutation exists in Alpha, Beta, Gamma, and Delta strains.

In addition, a variety of mutant strains also co-existed a mutation related to membrane fusion, D614G, which can promote the virus to fuse with human cell membranes more easily. This time it also appeared in "Omi Keron".

　　Regarding what characteristics other mutations or mutation combinations will bring to "Omi Keron", further follow-up studies are needed.

　　There are also many mutations that will have weakened effects.

For example, a paper published by Wang Youchun's team from China Food and Drug Control Research Institute in Cell last year showed that some mutants are less infectious, such as V341I, D405V, V503F, P521S, etc., while amino acids at N331 and N343 The lack of glycosylation will greatly reduce the infectivity of the virus.

　　In general, “the more mutations are not necessarily related to the worsening of the virus.” Tong Yigang said.

　　Three questions: Are vaccines and drugs still effective?

　　Among the mutation sites of "Omi Keron", E484A has also attracted widespread attention.

　　"The mutation at position 484 is more critical because it may give the virus the ability to evade neutralizing antibodies." Tong Yigang said that based on previous studies, a single point mutation in this place can escape the neutralization of multiple monoclonal antibodies to varying degrees. And the effect, which means that the effect of some targeted vaccines or neutralizing antibody drugs may be weakened.

　　Will it lead to the failure of existing or under-development drugs or vaccines?

　　"Drugs have many mechanisms of action, and not all of them are related to S protein." Tong Yigang said that by comparison, chemical drugs will be less affected.

　　In terms of vaccines, Tong Yigang said that there are many types of antibodies in the body. If the S protein structure of the virus undergoes major changes, a new structure of antibodies may be needed to effectively neutralize it.

　　At the previous press conference on the Joint Prevention and Control Mechanism of the State Council, Zhang Yuntao, chief scientist of Sinopharm Group China Biotechnology, said that inactivated vaccines contain more antigenic components of the virus, and relatively speaking, they have better broad-spectrum protection and will be more resistant to mutations. Better.

It can be seen that the antibodies produced by inactivated vaccines are more diverse, and maintaining high titers of antibodies is still an effective means to avoid viral infections.

　　"The neutralizing antibody will increase dozens of times after the third and fourth shots of vaccines. How often will the vaccine be given after that? It still needs further research and testing to prove it." Tong Yigang said.