Is the new coronavirus artificial? Was it leaked from the laboratory? Latest evidence is here
The epidemic of the new crown virus is spreading globally, and there is no conclusion as to the origin of the virus. Today, six top scientists from the United States, the United Kingdom, and Australia published articles in the authoritative Nature Medicine journal, pointing out the possible source of the virus.
The new crown virus has 3 different characteristics
Through genetic analysis of the new coronavirus and comparing it with other known coronaviruses, scientists have discovered that the new coronavirus has three significant characteristics.
1. The combination with ACE2 is unique
Like the SARS coronavirus, the new coronavirus also binds to human ACE2, and then enters human cells to cause infection.
It can be simply understood that there is a key on the virus, which can open the lock on our human cells. After the virus opens the door, it enters the human cell.
However, analyzing the receptor binding domain (RBD) of the SARS coronavirus and the new coronavirus, we found that the structure of the receptor binding domain of the two viruses is very different.
The receptor binding domain has 6 amino acids. Compared with the SARS binding domain, the new coronavirus has 5 amino acids that are different.
In other words, the new coronavirus uses a different combination to enter human cells. Even though it is the same lock, the key of the new coronavirus is different from the key of the SRAS coronavirus.
2. There is a multi-base restriction site on the S protein
S protein is also called spike protein, which is a prominent protein on the surface of coronavirus. The receptor binding domain of the new coronavirus is also on the S protein. The S protein has two subunits, S1 and S2.
Studies have found that there is a multi-base restriction site (RRAR) at the junction of the S1 and S2 subunits of the S protein.
This allows Flynn and other proteases to recognize this restriction site and cut the S protein, which may open the structure of the S protein.
The exact role of the restriction site is unknown, and further research is needed, but similar structures have been observed in influenza viruses. The restriction site may increase the pathogenicity of the new coronavirus.
3. O-linked glycan structure
Compared with other coronaviruses, the S protein of the new coronavirus has an O-linked glycan structure. O-linked glycan structure, carbohydrates can be linked to proteins.
The specific role of the O-linked glycan structure is unknown, but a "mucin-like domain" can be generated to protect some potential epitopes or key amino acids on the S protein of the new coronavirus.
It is currently known that some viruses use mucin-like domains as sugar chain barriers for immune evasion. In other words, the O-linked glycan structure may help the new coronavirus to provide protection from immune attacks.
Please remember that these three different characteristics of the new coronavirus are very important for speculating on the origin of the virus.
The new coronavirus is most likely to come from natural selection rather than artificial synthesis.
There are two main reasons for COVID19 to be natural rather than artificial:
i. The unique receptor binding method
As we said earlier, although the new coronavirus also enters human cells through ACE2, the receptor binding domain of the new coronavirus is different from the SARS virus.
This binding method has not appeared before. In the computer model, this combination method Is not ideal.
In other words, the new coronavirus has a strong ability to bind ACE2, but the combination method is something we have not seen before.
If it is a synthetic virus, we are unlikely to adopt such a combination method that has never appeared before. The possibility of natural mutation of the virus is great.
ii. No evidence of gene editing was found
If the new coronavirus is artificially synthesized and we have carried out genetic manipulations, we should see the reverse genetics system used for the coronavirus=. However, this is not the case, because genetic data shows that the new coronavirus is not derived from any previously used Virus skeleton.
Based on these two most important evidences, scientists speculate that the new coronavirus is not artificially synthesized, but caused by natural mutations, and suggests two possibilities.
2 possible origins of the new coronavirus:
i. Natural selection among animal hosts
The new coronavirus spreads between animals first, and has mutated during the process of transmission.
It has obtained all three unique characteristics of the new coronavirus: a unique binding method with ACE2, a unique receptor binding domain; a multi-base restriction site Point; O-linked glycan structure.
However, no such animal host has been found. Although the coronavirus RaTG13 from the Chinese chrysanthemum bat and the new coronavirus have about 96% similarity at the whole genome level, the receptor binding domains of the two are quite different.
This suggests that it may not effectively bind to human ACE2. In other words, the coronavirus in bats cannot directly infect humans.
A coronavirus was found in Malayan pangolins, which showed a high degree of similarity to the receptor binding domain of the new coronavirus, including six key amino acids.
However, no matter whether it is a pangolin or a coronavirus in bats, they do not have polyalkaline enzymes. Cut site.
In other words, we may not have found the intermediate host of the new coronavirus. It may be an organism with a higher population density and the ACE2 gene is similar to a human homologous protein.
Only in this way can mutations occur in the continuous passage. , To obtain the multi-base restriction site.
If this is the case, the new coronavirus may have always existed in certain animals in nature, even if we defeated the new coronavirus this time. Then, the new coronavirus may make a comeback, because we have not yet found this intermediate host.
ii. Spread mutations from person to person
There is also a possibility that the ancestors of the new coronavirus may directly infect humans. Then it spreads from person to person, and in the process of transmission, it adapts to humans and produces genetic mutations.
We found a type of coronavirus in the body of pangolin, which has the same receptor binding domain as the new coronavirus, and theoretically, it can infect humans.
If this is the case, then the virus spreads between humans first, and mutations have occurred in the process, resulting in the characteristics of polybasic restriction sites.
Once the virus has acquired these adaptations, it will bring about an outbreak of the epidemic, which will then produce a large enough and abnormal cluster of pneumonia cases, the medical monitoring system is triggered, and the virus is found.
If this is the case, if the epidemic can be controlled, the new coronavirus epidemic is unlikely to break out again, because genetic mutations are random, and it is difficult to obtain such mutations again.
Is the laboratory leaking the new crown virus intentionally or unintentionally?
Is it possible that the laboratory leaks? Many laboratories have been cultivating coronaviruses and conducting some research.
However, in the process of in vitro or in vivo cultivation, it is very difficult to obtain the three characteristics of the new coronavirus. There has never been a similar report before.
Theoretically, in the process of in vitro culture, mutations in the receptor binding domain may occur, resulting in the receptor binding domain of the new coronavirus.
However, we have found coronaviruses with almost the same binding domain in pangolins, which provides a more powerful and concise explanation for how the new coronavirus obtains these RBDs through recombination or mutation.
At the same time, the presence of polybasic restriction sites or O-linked glycan structures also opposed the hypothesis based on laboratory culture. This is because only when the low pathogenic avian influenza virus is spread in cell cultures or animals for a long time, can the polybasic restriction site be produced.
In addition, if the new coronavirus is really produced through cell culture or animal passage, it is necessary to isolate the progenitor virus with very high genetic similarity in advance and pass it in large numbers in animals with human homologous ACE2 receptors, but this work has never been done before. Report.
At the same time, it is unlikely to obtain an O-linked glycan structure, because this mutation usually indicates the involvement of the immune system, which does not exist in vitro.
Based on the current research results, the we may believe that the new coronavirus does not come from artificial synthesis or laboratory leaks, but from nature.