The virus that was waiting for an opportunity to move is once again making its way through human society. Since the outbreak, scientists around the world are working hard to piece together the puzzle of the new coronavirus. By determining the full genome sequence and extracting the viral strain, scientists have deciphered the unlocking code of the new coronavirus in the shortest possible time. The “antidote” for the new coronavirus is also emerging, with the vaccine entering animal testing. From the laboratory to the hospital bedside, the light was beginning to dawn. But where the virus came from, and who was the first “patient zero” to be infected, there are still too many unknowns and controversies that will take time to find answers. The virus attacked the unknown virus appeared in 2019. Until today, Lin Hua (a pseudonym) lying on a bed in Wuhan Jinyintan Hospital still does not know why she was attacked by the virus. She only remembers that the symptoms first appeared in December, holding her breath, coughing, lacking strength in her body and having a high and low body temperature. It was the virus at work in her body. Before it broke Linhua, it had broken through three lines of defense in her body: first, it penetrated the physical barrier of skin, mucous membranes and secretions, then it bypassed the phagocytes that were on daily “patrol” to find and “eat” the invading virus, and then it broke free of the immune cells. The virus then bypasses the phagocytes that routinely “patrol” the lungs to detect and “eat” the invading virus, and then breaks free of immune cells. Ultimately, it does so by recognizing the ACE2 protein located on the surface of lung epithelial cells – the “doorknob” for the neocoronavirus to invade the body, which the virus grabs via the stinger protein (S protein), thus opening the door to enter the cell –The virus enters the human cell and uses the cell’s energy to reproduce itself. Like a parasite, the virus is never content to stay in one infected person, but wants to attach itself to as many hosts as possible. One sneeze, one close conversation, and the virus can be passed from one person to another, to a group of people, in such a geometric frenzy of replication to survive. Available epidemiological investigations suggest that such human-to-human transmission of the virus has been occurring since at least mid-December of last year. But at the time, the danger went unnoticed. Three, five, ten …… until infected people became ill one after another and walked into the hospital. Fever, cough, “big white lung”, patients with unusual and similar symptoms to each other, which caused the Hubei Provincial Hospital of Integrative Medicine doctor Zhang Jixian alert. After seeing several patients in a row, she “sounded the alarm” at the end of December. Capturing the pathogen On the last day of 2019, as the unknown virus “pneumonia of unknown origin” entered the public eye, researchers began trying to decipher the genetic data of the virus. The viral genome, which is the code of life of the virus. With the help of molecular biotechnology, pathologists can obtain the genome sequence of the virus in a short period of time by measuring specimens such as nasopharyngeal swabs and bronchoalveolar lavage fluid of virus-infected patients. Such a decipherment was done as early as January 2, 2020. on January 2, at 12:00 noon, the CDC Virus Institute received for the first time specimens from the Hubei Provincial CDC for four cases of the Wuhan unexplained viral pneumonia outbreak. Before that, the research team in far away Shanghai got the specimens earlier than the CDC. On December 26, 2019, the Shanghai Public Health Clinical Center collected one specimen of patients with unexplained fever from the Wuhan Central Hospital and the Wuhan CDC. The first expert to publicly release the full gene sequence of the novel coronavirus, Zhang Yongzhen, an adjunct professor at the Shanghai Public Health Clinical Center, explained that the team has long collaborated with Wuhan Central Hospital and Wuhan CDC on research projects, and this specimen was routinely collected for the project. This specimen came from a 41-year-old male working at the South China Seafood Market, who developed the disease on December 20 and went to Wuhan Central Hospital for consultation and hospitalization after six days of fever and cough. Four days later, the Wuhan Institute of Virus, CAS, received a sample of pneumonia of unknown origin from Wuhan Jinyintan Hospital on the evening of December 30, 2019. Subsequently, researchers from the Wuhan Institute of Virology, CAS, the Institute of Virology, CDC, and the Shanghai Public Health Clinical Center were busy all night in the laboratory and obtained the full genome sequence of the virus in the early hours of January 2, January 3, and January 5, respectively. The genomic results of the three teams proved that this is a brand new coronavirus that has never been found in humans. It is the seventh member of the coronavirus family, unlike the already “well-known” SARS and MERS viruses. Obtaining the full genome sequence is only the first step in isolating the virus from the specimen to uncover the real “culprit”. Normally, finding the nucleic acid and genome of a pathogen from a patient can be done in a short period of time, but isolation of the pathogen takes several weeks. This time it didn’t take long. According to Xu Jianguo, head of the expert group for the preliminary evaluation of pathogen test results and a member of the Chinese Academy of Engineering, the virus was isolated from one positive patient sample in the laboratory as of 21:00 on January 7. And the Wuhan Institute of Virus of the Chinese Academy of Sciences seems to have completed this step earlier. According to its official website, the virus institute has isolated the virus strain on January 5. On January 9, officials announced that the pathogen of the “unexplained pneumonia” was initially determined to be a new coronavirus. The unknown virus that struck Lin Hua was “caught in the act”. On January 11, Professor Edward Holmes of the University of Sydney, a member of Yongzhen Zhang’s team, released the full genome sequence of the novel coronavirus at the National Center for Biotechnology Information (NCBI) in the United States, announcing the “ID number” of the novel coronavirus to the world for the first time. “ID number”. On the same day, Chinese officials also announced that they would share the virus gene sequence with the World Health Organization. What is the virus, scientists found the answer, but where exactly did the virus come from and how did it take a critical step in nature to step into human society? Obtaining the full viral gene sequence paves the way forward for such virus traceability. By using the genome sequence of the novel coronavirus and comparing the genes and functions of the SARS virus and coronavirus found in humans and different animals, we can not only understand its “proximity” to other coronavirus family members such as SARS, but also compare its similarity to the coronavirus in animals and speculate on its It is also possible to compare its similarity to coronaviruses in animals and to speculate about its origin. Who is the natural host of the new coronavirus in nature? Several pieces of scientific evidence now point to bats. Tiny bats are actually a “concentration camp” for the virus. Professor Jin Qi, director of the Institute of Pathogen Biology at the Chinese Academy of Medical Sciences, explains that bats are the natural hosts of many viruses, including Ebola, Marburg, and rabies viruses. Due to their special immune system, bats carry viruses but rarely develop disease. During their long evolutionary history, bats have become the natural hosts of hundreds of viruses. In a study by the team of Zhengli Shi and Peng Zhou at the Wuhan Institute of Virology, Chinese Academy of Sciences, the new coronavirus is 96% homologous to a bat coronavirus found in Yunnan. Studies by three institutions, including the Shanghai Pasteur Institute of the Chinese Academy of Sciences and the Military Medical Research Institute, similarly speculated that the natural host of the new coronavirus may be bats. On January 24, a research paper published by the Chinese CDC and several other institutions reconfirmed this conclusion. The paper disclosed that on December 31, the CDC had sent a rapid response team to Wuhan to assist the local health authorities in their investigation. The team found 86.9% nucleic acid sequence identity between the novel coronavirus and a SARS-like coronavirus (bat-SL-CoVZC45,MG772933.1) known to have been isolated from bats through analysis of samples from three Wuhan Jinyintan Hospital patients. This finding was included in the fourth edition of the National Health Commission’s protocol for the treatment of new coronavirus pneumonia. Who is the intermediate host But whether there is an intermediate host from bats to humans, and who plays this role, scientists are still searching. Xiao Yonghong, a professor at the First Hospital of Zhejiang University School of Medicine and the State Key Laboratory of Infectious Disease Diagnosis and Treatment, explained that under normal conditions, the bat virus does not directly infect humans, but requires an intermediary, usually a mammal, to infect people. The “springboard” in the middle is the intermediate host. For example, he said, the SARS virus intermediate host is a civet, and the MERS virus intermediate host is a camel. In his research with Peking University professor Zhu Huaiqiu’s team, the deep learning algorithm hypothesized that the intermediate host could be a mink. However, he cautioned that this is only a research idea for pathogenologists, and everything has to be studied in the laboratory to reach a final conclusion. After the mink, the pangolin was also “nominated”, and in the early hours of February 7, South China Agricultural University released news that the pangolin may be a potential intermediate host for the new coronavirus. The researchers gave more evidence: by analyzing more than 1000 macro-genomic samples, the pangolin was targeted as a potential intermediate host. In turn, the positive rate of beta coronavirus in pangolin was found to be 70%; and the virus was observed to have a typical coronavirus particle structure under electron microscopy; in addition, the genomic analysis revealed that the isolated virus strain had 99% sequence similarity to the strain currently infecting humans. The findings of this study also came into official view. Wu Yuanbin, director of the Department of Social Development Science and Technology of the Ministry of Science and Technology, revealed that the Ministry of Science and Technology is organizing relevant research teams to validate the above research findings. Just on February 18, a new study locked the pangolin again. A research article published in BioRxiv by Professor Guan Yi, director of the State Key Laboratory of Emerging Infectious Diseases at the University of Hong Kong, and Professor Hu Yanling of Guangxi Medical University, provides the latest evidence that pangolin is the animal host of a novel coronavirus. The study, which sequenced the genome sequence of Malay pangolin smuggled from southern China, reached the important conclusion that these newly discovered coronaviruses in pangolins have 85.5% to 92.4% similarity to the new coronavirus that infects humans. The pangolin should be considered as a possible intermediate host for the new coronavirus. Beyond the animal traceability, the origin of the new coronavirus is also shrouded in fog. A number of preliminary studies by the CDC have pointed the finger at the South China seafood market, and “the virus first appeared in the South China seafood market in Wuhan” has almost become a social consensus. But in late January, the international medical journal The Lancet published a study whose findings seem to contradict this. The study involved a number of clinical medical experts, including Cao Bin, director of the Department of Respiratory and Critical Care Medicine at the Sino-Japanese Hospital, and Zhang Dingyu, president of Wuhan Jinyintan Hospital. The study confirmed that the earliest case of novel coronavirus pneumonia developed on December 1, that no link was found between the case and the South China seafood market, and that three of the first four infected individuals had no history of South China market exposure. In a report in Science, Cao Bin bared his uncertainty, “South China seafood markets do not appear to be the only place where the virus originated; truth be told, we’re not quite sure where exactly the virus came from yet.” However, in the latest official statement, South China Seafood Market is still the most likely place of origin. on February 15, Wu Yuanbin reiterated in a press conference the conclusions of previous studies: the Chinese CDC obtained from the South China Seafood Market and other fresh markets in Wuhan, 585 environmental samples, 33 presented positive samples of the new coronavirus, 31 of which came from operating wildlife South China Seafood Market West. “These data suggest that the outbreak may be related to the wildlife trade.” Wu Yuanbin said. Disappearing “Patient Zero” The first patient infected with the virus carries a lot of key information for a new outbreak of an infectious disease. The public refers to this patient as “Patient Zero”. Because of its own mystery, the legend of “Patient Zero” was once prevalent. Zhejiang University Institute of Life Sciences Professor Wang Liming said, “patient zero” corresponds to the academic term “primary case”, commonly understood as in this patient “a virus from animals into the human body for the first time The patient is the first time a virus has entered the human body from an animal,” he said. The identification of “patient zero” is crucial to the traceability of the virus and the spread of the outbreak. According to Ning Yi, a professor at Peking University’s School of Public Health, we do not currently have confirmation of the information that the new coronavirus has passed from animals to humans, “If Patient Zero was exposed to what we suspect are common exposures such as bats, civets, and pangolins, but we don’t find them, others could develop the disease if exposed to such exposures. That’s what we’re looking for in Patient Zero.” The earliest known patient developed the disease on Dec. 1, 2019. Wuhan Jinyintan Hospital recorded the patient’s medical history, and in the recollection of Wu Wenjuan, director of the hospital’s intensive care unit, it was a man in his 70s with cerebral infarction and dementia who barely left his home and lived close to the South China Seafood Market, but never went there. How did he get infected without leaving home? Is this patient a real “patient zero”? Were there others before him who were infected but never sought medical attention? According to a report released by the CDC on February 17, 104 people had been infected in Wuhan and Hubei by December 31, 2019. Whether these additional patients will reveal more secrets about the early stages of the outbreak is subject to further examination. However, we must be prepared – the search for “patient zero” may be an impossible task. To date, AIDS, Ebola, SARS, and other epidemics have never clearly identified a “patient zero” in the strictest sense of the word. The search for the “antidote” outside the sound of controversy, the other way, researchers are looking for a new coronavirus drug. In contrast to the development of new drugs, “new use of old drugs” is the first aid in times of crisis. The earliest hope is the anti-AIDS drug “klezhi” (lopinavir/ritonavir). As a protease inhibitor, Klonopin was able to reduce the HIV load by producing non-regenerative, immature HIV particles. As a number of experts have suggested that Crestor may be effective in Newcastle pneumonia, and the national treatment protocol mentions that Crestor may be tried, this antiviral drug, which has been available for more than 20 years, had its “highlight moment” in the 2020 pneumonia epidemic. Zhang Dingyu, president of Wuhan Jinyintan Hospital, the designated hospital for patients with Newcastle pneumonia, is one of the proponents of Krylon. He is conducting a comparative trial with 198 patients, some taking Krylon and others taking a placebo, to determine the effect of Krylon on the treatment of Newcastle pneumonia. “So far, it looks like kryptozole reduces mortality and decreases the incidence of critical cases.” In his observations, the rate of New Crown Pneumonia infection was reduced in AIDS patients taking the drug: more than 1,000 cases were tracked, and only 3-5 cases contracted New Crown Pneumonia. However, Li Taisheng, an AIDS treatment expert and director of the Department of Infectious Diseases at Peking Union Medical College Hospital, took a wait-and-see attitude, “When SARS and MERS epidemic broke out, there were mentions of treatment with AIDS drugs, but none of them were supported by clinical data.” The results of rigorous scientific trials are needed to determine whether they are effective. Also waiting for clinical data are three drugs: chloroquine phosphate, famipiravir, and raltegravir. Previously, they were used for the treatment of malaria, influenza and Ebola hemorrhagic fever, respectively. Currently, clinical trials have been initiated for the above 3 drugs in Wuhan and other places. Patients, the public, doctors and scientists are eagerly waiting for them. While looking for effective drugs, people see vaccines as another “lifesaver”. Inactivated vaccines, MRNA vaccines, recombinant protein vaccines, viral vector vaccines, DNA vaccines, new crown vaccines with different technologies are being developed globally, and in China, several vaccines have entered animal testing. Researcher Yan Jinghua’s team at the Institute of Microbiology, Chinese Academy of Sciences, is working on the development of a recombinant protein vaccine for New Crown, and the previous experience in MERS vaccine development has helped in this development. In order to get the vaccine on the market as soon as possible, the team is trying to shorten the R&D cycle as much as possible. In the past, a trial ended to see the results before a second trial was conducted, but now many trials have been changed to advance simultaneously. She revealed that the vaccine development is progressing smoothly and is being tested in animals to observe the immunization effect, followed by safety tests. When will the vaccine be developed successfully? The Ministry of Science and Technology gave a timeline on February 22: clinical trials will be declared in late April at the earliest. This is a harsh reality that people must accept. For a newly discovered pathogen, successful vaccine development and eventual mass production to the general public can take months to complete. And this is already running the fastest pace compared to vaccine development that usually takes years or even 10 years to count. Content source: Xinjing News