However, this data does not make people believe that pangolin is the intermediate host. After all, the virus found in civet cat, the intermediate host of SARS, has a 99.8% gene sequence consistency with that of human SARS virus. However, there is also some evidence to support pangolin as an intermediate host.
Although some foreign research institutions claim that bats carrying new coronavirus may directly infect people, they havent shown excellent evidence and published new papers at present. At present, the evidence of bat coronavirus directly infecting people is mainly the papers published by Shi Zhenglis team at the end of 2017 and the beginning of 2018. One of the papers directly targeted that the source host of SARS virus is Chinese chrysanthemum head bat. The paper introduced 6 Three villagers were seropositive, and predicted that the bats may cause SARS like diseases after being infected with SARS related coronavirus.
At present, there are several problems that need to be solved urgently, whether it is the direct infection of bat virus to human beings or the pangolin as an intermediate host participating in the recombination and transfer of new coronavirus.
Why is the receptor binding domain of new coronavirus more similar to pangolin coronavirus?
According to the published gene sequence, the new crown virus is more similar to the bat cov ratg13 (BAT cov ratg13) found in Yunnan Province by Shi Zhengli. The similarity between the two gene sequences is 96.2%, while the consistency between the new crown virus and the new crown virus in pangolin is about 90%.
Zhao Suwen, a researcher at ihuman Research Institute of Shanghai University of science and technology, pointed out that it is bat coronavirus ratg13 that ranks first and pangolin coronavirus that ranks second.
But there is also evidence against the conclusion that bat coronavirus is more similar to new coronavirus. In terms of receptor binding domain (RBD), which is the main role of coronavirus invading human body, pangolin coronavirus is more similar to new coronavirus. Guan Yis team paper showed that Guangdong pangolin coronavirus and new coronavirus had the same amino acid on the five key residues of RBD, while bat coronavirus (ratg13) had only one amino acid. Chen Jinping and others analyzed the ACE2 receptor and found that the pangolin was highly consistent with the ACE2 receptor in human body.
According to Matthew Wong of Baylor medical school in Houston, it seems that the recombination between the coronavirus strain found in pangolin and the bat virus strain produces the receptor binding domain of the new coronavirus. However, Guan Yi and others do not tend to have reorganization, but think there is convergence evolution.
After sequencing the new coronavirus, many scientists have found a very important feature. Spike protein (or spike protein, spike protein) is the crown tip of coronavirus. The receptor binding domain in this article is on the s egg white, responsible for binding with the receptor, so that the virus can enter the cell. u2014u2014Reporter note) there may be a furin protease cleavage site.
Gao Shan and others from Nankai University reported this important variation for the first time in the world. Their paper was submitted to the website of chinaxiv, a preprint of the Chinese Academy of Sciences on February 2. According to Gao Shans paper, this finding suggests that Wuhan 2019 coronavirus may have a significant difference in the infection pathway from SARS coronavirus, which may adopt the packaging mechanism of other viruses such as HIV and mouse hepatitis coronavirus, but is different from most other beta coronaviruses such as SARS. Due to the change of packaging mechanism, the S protein of Wuhan 2019 coronavirus has achieved higher efficiency of infecting cells, which may be one of the reasons why its transmission ability is greater than that of SARS coronavirus. In addition, some avian influenza viruses can also obtain a furin protease cut site through mutation, so as to improve their infection efficiency.
The Scripps Research Institutes Christian Anderson team explained that this cut site can enhance cell and cell fusion, but will not affect the viruss entry. Multiple cleavage sites allow for efficient cleavage of furin and other proteases, as well as rapid replication and transmission of the virus.
In other words, the new coronavirus is packaged with HIV, which is as efficient as avian influenza. This is not possessed by SARS virus, nor found in bat coronavirus and pangolin coronavirus. Some researchers think that the new coronavirus has more furin cleavage sites than other closely related viruses, and the similarity between receptor binding domain and bat coronavirus, which is more closely related to the whole, is not as good as pangolin coronavirus, which is further related to the whole. If we can obtain these uniqueness through natural evolution, it is very incredible..
Therefore, this also makes the new coronavirus artificial theory in the early stage of the disease. Novel coronavirus is a serious conspiracy theory. It has been refuted by dozens of scientists in the world. They issued a document on the lancet, saying, severely condemning the conspiracy theories of some new networks around the world, especially those conspiracy theories that claim that the virus is not from nature but from some artificial chemical .
Considering the bat hibernation season, how is patient zero infected?
The outbreak of novel coronavirus pneumonia was first reported in Wuhan, and the environmental and climatic characteristics of Wuhan were taken into account by researchers.
Before and after Shi Zhengli officially released bat cov ratg13 in Yunnan Province, Wu Guizhen and others from China CDC studied the bat coronavirus samples in the gene bank, and found that the sequence identity of the two kinds of bat SARS related coronaviruses collected in Zhoushan, Zhejiang Province, China was 88%. It was found that the source host of the new coronavirus might be bats, but some facts showed that another animal was in the process of It serves as an intermediate host between bats and humans. The study was published in the lancet.
The novel coronavirus pneumonia outbreak in late December 2019 was one reason why Wu Guizhen and others made this judgement. Most bat species in Wuhan were hibernating. In addition, they believe that bats are not sold or found in the South China seafood market, and there are various non aquatic animals (including mammals).
With the deepening of the research, the conclusion that originated in South China market is gradually questioned. In particular, Yu Wenbin, associate researcher of Xishuangbanna Tropical Botanical Garden of Chinese Academy of Sciences, and other researchers, based on the analysis of the whole genome data, found that multiple haplotypes appeared in other places (even abroad) were not found in the samples with a history of market contact in South China, and there was no evolutionary relationship, and even no haplotypes were found in Wuhan. The virus in South China market may have been imported in late November last year.
According to a paper published by Shi Zhenglis team at the end of November 2017, when conducting longitudinal monitoring of SARS related coronaviruses in a single cave in Yunnan Province, it was found that the coronaviruses in bat feces samples changed with sampling time. Generally, the positive rate in autumn (September and October) is higher than that in spring and early summer (April and may). They explained that this may be due to the emergence of a susceptible group of newborn bats, which do not have their own immunity after childbirth. In addition, the species of bats in the cave also changed in different sampling dates. The positive rate of bats in September 2012 reached 51.3%, when most of the samples came from the Chinese chrysanthemum head bat. But in May 2015, only three of the 145 samples were positive, and the three leaf hoof bat was the main species in the cave.
Outside of Wuhan, people in other places, especially in the tropics, have more opportunities to contact bats. In some parts of Southeast Asia, even the large and fleshy fruit bats are used as game. In 2015, Shi Zhenglis team found 6 SARS related coronavirus seropositive villagers in 4 villages near batdong, Xiyang Yi Township, Jinning District, Kunming City, none of whom had symptoms or had been exposed to SARS virus. One of them has been to Shenzhen. Fortunately, none of the six peoples oral and fecal swabs or blood cells were positive for viral nucleic acid. When researchers sample bats, they may also expose themselves to the blood and feces of bats. Tian Junhua, the center for Disease Control and prevention in Wuhan, once described that bat urine drips from head to body like raindrops and several times bat blood directly sprays on the skin, which increases the risk of bat virus infection.
These doubts may need to be answered by patient zero to determine what animal he is in contact with. Taking mers as an example, after cutting off the transmission of single humped camels to humans, the epidemic was quickly controlled. However, compared with the high transmission rate of mers virus, the new coronavirus increases the difficulty of traceability.
1. Identification of 2019 ncov related coronaviruses in Malayan pangolins from southern China;
2. Isolation and characterization of 2019 ncov like coronavirus from Malayan pangolins (isolation and identification of new coronavirus like viruses from Malaya pangolins);
4. Evidence of coronavirus recombination in pangolin origins of ncov-2019, presented by Matthew C. Wong et al. On February 7.
From the end of November 2017 to February 2018, Shi Zhenglis team published three papers in PLoS patterns, an American Journal of biology, and virological Sinica, an English journal of Wuhan Institute of Virology
5. The discovery of a rich gene pool of bat SARS related coronavirus was found in the origin of SARS coronavirus;
6. Longitudinal surveillance of beta coronavirus in fruit bats in Yunnan Province, 2009 u2013 2016;
7. Serological evidence of bat SARS related coronavirus infection in humans, China.