Recently, China's first anti-new crown virus special drug has been approved by the Food and Drug Administration.
Zhang Linqi, a leader in the research and development team and a professor at Tsinghua University School of Medicine, said in an interview that "the drug takes intravenous infusion and works immediately after being injected into the body." Messages are of concern.
China Youth Daily learned that the average age of the research and development team is less than 30 years old, consisting of 4 teachers, 11 doctoral and postdoctoral students.
On December 16, the official micro of "Tsinghua University" issued a long article to review the research and development process -
Back to the beginning of 2020, on January 12, the Chinese Center for Disease Control and Prevention, the Chinese Academy of Medical Sciences, and the Wuhan Institute of Virology of the Chinese Academy of Sciences submitted information on the genome sequence of the new coronavirus to the World Health Organization, and released it in the Global Influenza Shared Database (GISAID).
The similarity between the gene sequence of the new coronavirus and the genetic sequence of the SARS virus has alarmed Zhang Linqi, who has been deeply engaged in the research of new and sudden infectious disease viruses such as HIV, SARS, and MERS for many years.
He and Professor Wang Xinquan of Tsinghua College of Life Sciences, who works in the same research building, called each other almost at the same time - these two old partners who have been working together in the field of virus research for more than a decade agree that the new crown virus is not trivial and must be studied immediately.
Chinese New Year's Eve the night before, the passage from Han to Hubei was closed. On the night of Chinese New Year's Eve January 24, Zhang Linqi received a WeChat message from his old friend, Professor Zhang Zheng of the Third People's Hospital of Shenzhen - there are blood samples from patients recovering from new crown pneumonia in the Shenzhen Third Hospital!
January 25, the first day of the Lunar New Year. Zhang Linqi and Wang Xinquan, two old colleagues who have cooperated with VIRUS research such as SARS and MERS for more than ten years, Zhang Linqi and Zhang Zheng, have cooperated in HIV research. Beijing and Shenzhen, three people and two places, the research team gathered to go out.
Six days later, on January 31, after a day-and-night test, the high-quality protein reagents were "freshly baked" and immediately sent to the Shenzhen Third Hospital. In addition to meals and necessary rest, the researchers have hardly stepped out of the laboratory, and finally from the convalescent blood B cells of patients infected with the new coronavirus (SARS-CoV-2) in China, they have successfully "fished" out a total of 206 strains of anti-new coronavirus monoclonal antibodies with efficient neutralization ability!
On February 9, after overcoming the obstacles of poor logistics in the early stage of the epidemic, 206 antibodies and their coding genes were difficult to deliver to Tsinghua Garden in Beijing.
Zhang Linqi explains:
"Our work is to isolate the optimal monoclonal antibody against the new crown virus and its coding genes from these antibodies, that is, to select the most lethal 'warriors', get the genes of these 'warriors', and thus obtain a large number of replication of the most lethal antibodies of the fundamental template."
On March 5, the antibody evaluation work ushered in a new breakthrough! For the first time, the team identified the highly effective covid-19 neutralizing antibody P2C-1F11 (later named BRII-196), which is one of the key antibodies in later antibody combination therapy drugs.
After the successful finding of the "golden" antibody, cracking the antiviral mechanism of the antibody immediately became the next focus of the research. Only by truly understanding the mechanism can we crack the mystery of making antibody drugs.
In order to carry out more elaborate research on the mechanism of the new crown virus entering the human body, Zhang Linqi and Wang Xinquan need to use shanghai's more advanced high-precision equipment to carry out synchrotron radiation light sources and accurately use crystallography to analyze the body structure of the virus entering the cell.
In order to "outperform" the new crown virus, the team took a taxi overnight from Beijing to Shanghai, and the "human flesh" transported the crystal structure.
In the Shanghai laboratory late at night, this batch of crystals from thousands of miles away did not live up to the efforts and waiting of everyone. Zhang Linqi recalled: "In the transport of more than a dozen crystals, the last one flashed a particularly beautiful diffraction, so that we can clearly analyze what its structure is through computer data analysis, this process is so exciting!" ”
So far, Wang Xinquan and Zhang Linqi have successfully resolved the high-resolution crystal structure of the new crown virus into the human body, which is the world's first high-resolution resolution of the structural basis between the "key" and the "lock".
Zhang Linqi and Wang Xinquan immediately drafted the paper and submitted it to the journal Nature. On March 19, the journal Nature officially accepted, and on March 30, the team's scientific and technological research results "The Structure of the New Coronavirus Spike Protein Receptor Binding Domain and the Receptor ACE2 Complex" were published online. This is currently the most cited paper in the world in the field of research on the invasion of cells by the new crown virus.
On April 11, the research team determined the drug research and development ideas of BRII-196/BRII-198, the first antibody combination therapy in China, and with the support and help of the Ministry of Science and Technology, the National Health Commission, the Ministry of Education, the National Drug Review Center and the Food and Drug Administration, Beijing Municipality and other relevant departments, it formally cooperated with Tengsheng Huachuang and other enterprises to promote the drug development and clinical trials of antibody combination therapy.
On May 21, the Shenzhen Third Hospital suddenly experienced an import-related epidemic situation abroad, and for the first time in China, it encountered a patient infected with a British mutant strain. In the face of the new variant strain, the patient's condition develops rapidly, and in order to curb the progression of the patient's condition to the greatest extent, Zhang Zheng's team will focus on the BRII-196/BRII-198 antibody combination drug that has achieved good results in foreign clinical phase II trials.
With the approval of the expert group and the approval of the State Drug Administration, the Shenzhen Third Hospital successfully applied for emergency clinical drugs for antibody combination drugs, becoming the "first person to eat crabs" in the clinical treatment of new crown in China.
Yuan Jing, director of the Department of Infectious Diseases of the Third Hospital of Shenzhen, said: "What surprised us was that on the second day of medication, the patient's new coronavirus-specific antibodies showed a rise of hundreds of times, and the symptoms of persistent fever also improved quickly, as if there was a 'miracle drug'. ”
On August 25, the interim results of foreign phase III clinical trials were released, and the clinical data were surprising: compared with the placebo group, the hospitalization and mortality rate of the antibody treatment group were reduced by 78%, and the mutant strains remained active!
To date, the BRII-196/BRII-198 antibody combination is still the only drug worldwide that has evaluated the therapeutic efficacy of patients infected with mutant strains and obtained best-in-class data. So far, more than 800 patients have been treated with this antibody combination, and the clinical expert group and medical team have responded well, of which the patient with the oldest age of receiving the drug is 92 years old.
Once upon a time, it took 10 years or more for antibody drugs to be developed and put on the market, but the whole process of Zhang Linqi and his collaborative team to develop anti-covid-19 antibody drugs took only 18 months.
Humanity vs. the epidemic
A third winter is just around the corner
The world for
Demand for anti-COVID-19 drugs
It's getting more and more urgent
Professor Zhang Linqi said:
"This is a 'clash' between humans and viruses at the nanoscale.
It has no smoke of war, and it will triumph. ”
Hats off to the researchers!
Source: China Youth Daily (ID: zqbcyol Finishing: Chen Yanshan) comprehensive "Tsinghua University" official micro
Editor-in-charge: Qin Daixin
Proofreader: Du Xiaojin (Intern)