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Research on Evolutionary Source of COVID19 and Its Molecular Pathways


Research reveals the evolutionary source of Wuhan's new coronavirus and its molecular pathways​

On January 21, 2020, researcher Hao Pei, Shanghai Pasteur Institute, Chinese Academy of Sciences, Researcher Zhong Wu, National Engineering Research Center for Emergency Prevention and Control Medicine, Academy of Military Medical Sciences, and Researcher Li Xuan, Key Laboratory of Synthetic Biology, Center for Excellence in Molecular Plants, Chinese Academy of Sciences In cooperation, published a paper entitled "Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission" online in SCIENCE CHINA Life Sciences (English version of "Science China: Life Sciences").


Genetic evolutionary relationship between the SARS coronavirus and the MERS corona virus

This paper analyzed and explained the evolutionary source of the new coronavirus that caused the recent outbreak of pneumonia in Wuhan, and the genetic evolutionary relationship between the SARS coronavirus and the MERS coronavirus that caused the "SARS" epidemic in Guangdong in 2002. 

Through the calculation of the structure of Wuhan's new coronavirus spike- protein, it is revealed that the Wuhan new coronavirus spike- interacts with the human ACE2 protein and mediates the molecular pathway of human infection. 

Also Refer: Vaccine Development Encyclopedia

The results assessed the potential human infectivity of Wuhan's new coronavirus, and provided a scientific theoretical basis for confirming the source and transmission route of the infection as soon as possible, and formulating efficient prevention and control strategies.


Since December 2019, there has been a concentrated outbreak of pneumonia of unknown origin in Wuhan City, Hubei Province. The epidemiological investigation found that these successive cases of pneumonia are all related to the "South China Seafood Market" in Wuhan. 

Wuhan City organized multidisciplinary expert consultation and investigation, and used experimental testing and other means to identify the pneumonia epidemic in Wuhan as viral pneumonia. 

On January 8, 2020, a new type of coronavirus was initially confirmed as the pathogen of the epidemic.


 Similarities between Coronavirus and SARS of 2002

The outbreak of viral pneumonia in Wuhan has many similarities with the outbreak of SARS in Guangdong in 2002. Both occurred in winter, and the initial occurrence originated from contact with fresh live animals traded in animal markets. Caused by an unknown coronavirus pathogen. 

As of 18:00 on January 20, a total of 224 cases of pneumonia caused by the new coronavirus have been reported in my country, including 217 confirmed cases (198 in Wuhan, 5 in Beijing, and 14 in Guangdong).

7 suspected cases (Sichuan) (2 cases in Yunnan Province, 1 case in Yunnan Province, 2 cases in Shanghai, 1 case in Guangxi Zhuang Autonomous Region, 1 case in Shandong Province). 

Japan notified 1 confirmed case, Thailand notified 2 confirmed cases, and South Korea notified 1 confirmed case. 

There are 14 medical staff among the infected patients, and the new coronavirus is spreading from person to person and has a tendency to spread.


Research on Evolutionary Source of COVID19 and Its Molecular Pathways

On January 10, 2020, the first genome sequence data of Wuhan's new coronavirus was released. Later, the genome sequences of multiple new coronaviruses isolated from patients were released. 

These new coronavirus genome data provide first-hand information for the study and analysis of the evolutionary source and pathogenic pathogenesis of Wuhan's new coronavirus.


In order to understand the relationship between the Wuhan new coronavirus and the two coronaviruses that are known to infect people, the researchers of this paper analyzed the Wuhan new coronavirus genome and the 2002 SARS coronavirus and the Middle East respiratory syndrome MERS coronavirus. The whole genome of the virus was compared and found to have an average of 70% and 40% sequence similarity, respectively. 

Among them, the key spike genes (encoding S-proteins) between different coronaviruses and host cells have greater differences.


In order to analyze the evolutionary source and possible natural host of the Wuhan new coronavirus, the researchers used the Wuhan new coronavirus and collected a large amount of coronavirus data to conduct genetic evolution analysis. 

It was found that the Wuhan new coronavirus belongs to the genus Betacoronavirus (Betacoronavirus). Betacoronavirus is a protein-encapsulated single-stranded positive-stranded RNA virus that parasites and infects higher animals (including humans). 

In the position of the evolutionary tree, it is adjacent to the SARS (causing "SARS" in 2002) virus and SARS-like virus group, but it does not belong to the SARS and SARS-like virus group. 

What's interesting is that their evolutionary common outer group is a HKU9-1 coronavirus parasitizing fruit bats. Therefore, the common ancestor of Wuhan coronavirus and SARS/SARS-like coronavirus is a virus similar to HKU9-1. 

Since the evolutionary neighbors and exogroups of the Wuhan coronavirus are found in various bats, it is speculated that the natural host of the Wuhan coronavirus may also be bats. 

Like the SARS coronavirus that caused SARS in 2002, the Wuhan coronavirus is likely to have an unknown intermediate host vector during its transmission from bats to humans.

 Analysis of Mechanism and Pathway of the New Coronavirus

Due to the large genetic distance between Wuhan's new coronavirus and the 2002 SARS virus and the "Middle East Respiratory Syndrome" MERS virus, the author of the paper analyzed the mechanism and pathway of the Wuhan new coronavirus infecting people. 

The S-protein of SARS virus and the S-protein of MERS virus infect human respiratory epithelial cells by interacting with human ACE2 protein or DPP4 protein, respectively. 

The author first compared the host receptor interaction region (RBD region) of the Wuhan coronavirus with SARS and MERS virus S-proteins, and found that in the RBD region, Wuhan coronavirus is similar to SARS virus, but is very different from MERS virus. Therefore, the possibility of S-protein and DPP4 interacting to infect people is ruled out. 

However, there are also great difficulties in the interaction between the Wuhan coronavirus S-protein and human ACE2-the five key amino acids that have been proven to interact with the SARS virus S-protein and ACE2 have changed in four of the Wuhan coronaviruses.


In order to analyze this problem clearly, the author of the article used the calculation method of molecular structure simulation to conduct structural docking studies on the Wuhan coronavirus S-protein and human ACE2 protein, and obtained surprising results. 

Although 4 of the 5 key amino acids that bind to the ACE2 protein in the Wuhan coronavirus S-protein have changed, the changed amino acids have perfectly maintained the interaction between the SARS virus S-protein and the ACE2 protein as a whole. 

The original structure conformation. Although the new structure of Wuhan Novel Coronavirus interacts with the ACE2 protein due to a small number of missing hydrogen bonds (compared to the SARS virus S-protein and ACE2, the effect is reduced), it still achieves a strong binding free energy ( -50.6 kcal/mol). 

This result indicates that the Wuhan coronavirus infects human respiratory epithelial cells through the molecular mechanism of S-protein and human ACE2 interaction. 

The research results predicted the ability of Wuhan coronavirus to infect humans, and laid a scientific theoretical foundation for scientific prevention and control, formulation of prevention and control strategies, and development of detection/intervention techniques.


 Research Result on Wuhan Coronavirus

This research result is supported by the national major science and technology project of "Major New Drug Creation" (the research and development of new varieties of emergency medical drugs and its key innovation technology system), and the Shanghai Pasteur Institute of the Chinese Academy of Sciences and the National Emergency. 

The joint research was completed by the Engineering Technology Research Center of Prevention and Control Drugs and the Key Laboratory of Synthetic Biology of the Molecular Plant Excellence Center of the Chinese Academy of Sciences. 

The research also received support from the National Natural Science Foundation of China and the "Biological Resources Derivative Library" project of the Strategic Biological Resources Program of the Chinese Academy of Sciences. Xu Xintian, Chen Ping, and Wang Jingfang are the co-first authors.

Author's Bio

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