Experts have compared two distinct features of the new coronavirus genome, which provide ample evidence to conclude that the new coronavirus is unlikely to be a laboratory-engineered virus, but rather a product of the virus’s natural evolution. At the start of the outbreak, rumors have been growing that the new 2019 coronavirus has come from a laboratory leak. Recently, five foreign scientists in the virology forum “Virology” jointly published a paper on the 2019 new coronavirus genome data analysis, pointed out that the 2019 new coronavirus is not laboratory synthesis, nor is it a deliberatemanipulation of the virus. At present, the paper has not been formally peer reviewed.
The five scientists include Ian Lipkin, director of the Center for Infection and Immunization at Columbia University’s School of Public Health and known as the “virus hunter.” There are also four researchers in biology or immunology from the Scripps Institute in the Us, the University of Edinburgh in the United Kingdom, the University of Sydney in Australia and the University of Durham in the United States.
The paper points out that the genome of the 2019 new coronavirus has two distinct characteristics compared with other coronaviruses. The paper then analyzes why the 2019 new coronavirus is unlikely to come from laboratory synthesis, starting with these two characteristics.
The combination of S protein sand and receptor, unlike artificial prediction
The first feature of the 2019 new coronavirus is that, based on structural models and early biochemical experiments, the virus appears to be optimized to bind to human ACE2 receptors.
It is necessary to take a look here, after a previous study found that the 2019 new coronavirus and SARS virus are through the protrusion protein (S protein) and the human ACE2 receptor binding, mediated the virus into human cells.
Huang Bo, deputy director of the Institute of Basic Medicine of the Chinese Academy of Medical Sciences and deputy director of the Department of Immunology at Beijing Concord Medical College, said the S-protein is a protein located on the surface of the coronavirus, which is enlarged like a nail. ACE2 is a protein located on the surface of epithelial cells in the human lungs.
“The receptor binding domain (RBD) in sars virus and SARS-related coronavirus S protein is the most easily mutated part of the virus genome,” these foreign experts said. The six residues in these receptor binding domains appear to be critical to binding to the body’s ACE2 receptors and to determining the host range. “
The paper said that the 2019 new coronavirus S protein gene sequence 486 residue of phenylalanine, and SARS virus S protein gene sequence L472. In SARS viral cell culture experiments, L472 can mutate into phenylalalanine. Previous studies have predicted that this is the best way for the receptor binding domain of SARS virus to bind to the human ACE2 receptor. However, phenylalanine at this location is also present in some SARS-like coronaviruses in bats.
In addition, the 2019 new coronavirus receptor binding domain of several key residuals, unlike previous studies have described the best binding to the human ACE2 receptor. But new research suggests that the 2019 new coronavirus has a high affinity for the combination of ace2 in the human body.
What does that mean? “The S protein of the 2019 new coronavirus appears to be the result of a natural selection of human or similar ace2, resulting in a different optimal binding scheme than predicted. This is strong evidence that the new 2019 coronavirus is not a product of genetic engineering. The authors of the paper said.
Enzyme cutting sites on S proteins can be obtained through natural variation
The second feature of the 2019 new coronavirus is the insertion of 12 nucleotides on the highly mutant S protein of the virus, with a suspected enzyme cut site.
“Typically, the presence of such enzyme cutting sites is seen as a sign of artificial genetic engineering. But studies of the avian influenza virus have found that the virus can also obtain enzyme cut points during natural evolution. Takayama, an associate professor at Nankai University’s School of Life Sciences, said in an interview with Science daily.
As mentioned in the paper, this enzyme cut site can be obtained at the junction of two sub-bases of the avian influenza virus hemagglutinin (HA) protein in natural selection environments where the virus is rapidly replicated and spread, for example in highly dense chickens. The acquisition of enzyme cutting sites can also be observed after the influenza virus HA protein is repeatedly transmitted in cell culture or in animals.
The paper suggests that the enzyme cutting points in HA proteins can be converted into highly pathogenic avian influenza viruses by insertion or recombination. Similarly, a non-toxic isolate of the Newtown virus can gradually obtain an enzyme cut point at the connection of its fusion protein sub-base during the continuous transmission of chickens, thus becoming highly pathogenic.
“This means that once the enzyme cut point is obtained, these viruses are equivalent to an upgrade that has the potential to increase their ability to transmit.” Takayama said.
Echoing this foreign expert’s paper, as early as January 27, Takayama and a number of researchers in the Chinese Academy of Sciences science and technology paper pre-release platform ChinaXiv submitted a study found that the 2019 new coronavirus S protein may have the Furin protease cut point.
Takayama said their study found that the S protein of the 2019 new coronavirus may have a Flynn protease cut point, resulting in its infection mechanism different from most beta-coronaviruses such as SARS. As a result of changes in the infection mechanism, the 2019 new coronavirus has achieved higher efficiency in entering cells, which may be one of the reasons why it is more capable of transmitting than the SARS virus.
“We were also surprised to find that some avian influenza viruses can obtain Flynn protease cut sites through mutations, suggesting that natural mutations can introduce Flynn protease cut sites. Takayama said.
The production of O-polysaccharide structure, which usually requires the involvement of the immune system
“The new 2019 coronavirus is unlikely to emerge through laboratory operations of existing SARS-related coronaviruses. These foreign experts say.
Experts point out that if genetic manipulation is carried out, one can expect that one of several reverse genetic systems that can be used for beta-coronaviruses will be used. However, this is not the case, as genetic data show that the new 2019 coronavirus does not come from any previously used virus backbone.
These foreign experts have suggested two possible scenarios to explain the origin of the new 2019 coronavirus: the first is the result of natural selection in non-human animal hosts prior to the transfer of zoonotic infectious diseases, and the second is the result of natural selection in humans after the transfer of zoonotic infectious diseases.
So, does the lab have the ability to design or synthesize viruses? “Technically, there’s no problem. Takayama told Science and Technology Daily.
In this regard, this foreign paper is also analyzed. “Over the years, basic research has been conducted in several BSL-2 (Biosecurity Level 2) laboratories around the world on the transmission of bat SARS-like coronaviruses in cell culture and/or animal models. Examples of SARS virus escloser scored by laboratory personnel working in BSL-2 confined environments were also recorded. Therefore, we must consider the possibility of intentionally or unintentionally releasing the new coronavirus of 2019. The paper says.
But experts later questioned that possibility.
They point out that the production of the 2019 new coronavirus through cell culture or animal transmission requires prior separation of precursor viruses with high genetic similarities. Subsequent enzyme cutting sites require intensive transmission procedures in cell culture, or in animals with ACE2 receptors similar to humans, such as ferrets.
However, the 2019 new coronavirus S protein has three O-polysaccharide structures around the enzyme cut site due to the presence of enzyme cutting sites. “It is doubtful whether the production of the O-polysaccharide structure will occur in cell culture, as this mutation usually means the involvement of the immune system, which is not present in vitro. These foreign experts say.
Originally published as “Chinese and foreign scientists give genomics basis: new coronavirus is not laboratory synthesis”