China's first special anti-COVID-19 drug takes effect immediately after infusion! An article reviews this "war without gunpowder"

Recently, my country's first special drug against the new coronavirus was approved for marketing by the State Food and Drug Administration.

Zhang Linqi, a leader of the research and development team and professor at Tsinghua University School of Medicine, said in an interview that "the drug is administered by intravenous drip and takes effect immediately after being injected into the body." This news has attracted attention.

China Youth Daily learned that the average age of the research and development team is less than 30 years old, and it consists of 4 teachers, 11 doctors and postdoctoral students.

On December 16, the official microblog of Tsinghua University published a long article reviewing the 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 the genome sequence information of the new coronavirus to the World Health Organization and published it on the Global Influenza Sharing Database (GISAID).

The similarity between the genetic sequence of the new coronavirus and the genetic sequence of the SARS virus made Zhang Linqi, who has been deeply engaged in the research of new and emerging infectious diseases such as HIV, SARS, and MERS for many years, suddenly alert.

He and Professor Wang Xinquan of the School of Life Sciences at Tsinghua University, who worked in the same research building, called each other almost at the same time. The two old partners, who have been working together in the field of virus research for more than ten years, agreed that the new coronavirus was of great significance and must be studied immediately.

The night before New Year's Eve, the channels leaving Wuhan and Hubei were closed. On January 24, New Year's Eve, Zhang Linqi received a WeChat message from his old friend, Professor Zhang Zheng of Shenzhen Third People's Hospital - Shenzhen Third Hospital has blood samples from recovered patients of COVID-19!

January 25th, the first day of the Chinese New Year. Zhang Linqi and Wang Xinquan, two old colleagues who have worked together on SARS, MERS and other viruses for more than ten years, and Zhang Linqi and Zhang Zheng, good friends who have collaborated on HIV research. The research team of three people in Beijing and Shenzhen gathered to set off.

Six days later, on January 31, after round-the-clock testing, high-quality protein reagents were "freshly produced" and immediately sent to Shenzhen Third Hospital. Except for meals and necessary rest, the researchers hardly stepped out of the laboratory, and finally successfully "fished" out a total of 206 strains of anti-new coronavirus monoclonal antibodies with high neutralizing ability from the blood B cells of patients infected with the new coronavirus (SARS-CoV-2) in China!

On February 9, after overcoming the many logistical obstacles at the beginning of the epidemic, 206 strains of antibodies and their encoding genes were delivered to Tsinghua University in Beijing with difficulty.

Zhang Linqi explained:

"Our job is to isolate the best monoclonal antibodies and their encoding genes against the new coronavirus from these antibodies, that is, to pick out the most lethal 'warriors', obtain the genes of these 'warriors', and thereby obtain the fundamental template for mass replication of the most lethal antibodies."

On March 5, the antibody evaluation work ushered in a new breakthrough! The team identified for the first time the highly effective COVID-19 neutralizing antibody P2C-1F11 (later named BRII-196), which is also one of the key antibodies in the specific drug of antibody combination therapy.

After successfully finding the "golden" antibody, deciphering the antibody's antiviral mechanism immediately became the next research focus. Only by truly understanding the mechanism can we decipher the secret of making antibody-specific drugs.

The laboratory's equipment conditions are limited. In order to conduct more detailed research on the mechanism of the new coronavirus entering the human body, Zhang Linqi and Wang Xinquan need to use Shanghai's more advanced high-precision equipment for synchrotron radiation light sources, and use crystallographic methods to accurately analyze the structure of the virus entering cells.

In order to "outrun" the new coronavirus, the team took a taxi from Beijing to Shanghai overnight and transported the crystal structure "humanly".

In the late night of the Shanghai laboratory, this batch of crystals from thousands of miles away did not disappoint everyone's efforts and waiting. Zhang Linqi recalled: "Among the dozen crystals transported, the last one flashed a particularly beautiful diffraction, which allowed us to clearly analyze its structure through computer data analysis. This process was so exciting!"

At this point, Wang Xinquan and Zhang Linqi have successfully analyzed the high-resolution crystal structure of the new coronavirus entering the human body. This is the first time in the world that the structural basis between the "key" and the "lock" has been analyzed with high resolution.

Zhang Linqi and Wang Xinquan immediately drafted a paper and submitted it to the journal Nature. On March 19, Nature officially accepted it, and on March 30, the team's scientific research results, "The structure of the complex between the receptor binding domain of the spike protein of the new coronavirus and the receptor ACE2," were published online. This is currently the most cited paper in the world in the field of research related to the invasion of new coronavirus into cells.

On April 11, the research team determined the drug development ideas for my country's first antibody combination therapy BRII-196/BRII-198, and with the support and help of the Ministry of Science and Technology, the National Health Commission, the Ministry of Education, the National Drug Evaluation Center and the State Food and Drug Administration, Beijing Municipal Government and other relevant departments, officially cooperated with companies such as Tengsheng Huachuang to promote the drug development and clinical trials of antibody combination therapies.

On May 21, Shenzhen Third Hospital suddenly encountered an epidemic related to overseas importation, and China encountered patients infected with the British variant for the first time. Faced with the new variant, the patient's condition progressed rapidly. In order to curb the progression of the patient's condition to the greatest extent, Zhang Zheng's team focused on the BRII-196/BRII-198 antibody combination drug, which had achieved good results in phase II clinical trials abroad.

With the approval of the expert group and the National Medical Products Administration, Shenzhen Third Hospital successfully applied for emergency clinical use of the antibody combination drug, becoming the first to try out clinical treatment for the new coronavirus in China.

Yuan Jing, director of the infectious disease department at Shenzhen Third Hospital, said: "What surprised us was that on the second day of taking the medicine, the patient's coronavirus-specific antibodies increased by several hundred times, and the persistent fever symptoms also improved quickly, as if it had the effect of a 'magic drug'."

On August 25, the interim results of the overseas Phase III clinical trial were announced, and the clinical data were surprising: compared with the placebo group, the hospitalization and mortality rates of the antibody treatment group were reduced by 78%, and it still remained active against mutant strains!

To date, the BRII-196/BRII-198 antibody combination is still the only drug in the world that has been evaluated for its therapeutic effect on patients infected with variant strains and has obtained the best data of its kind. So far, more than 800 patients have received treatment with this antibody combination, and the clinical expert group and medical team have given good feedback. Among them, the oldest patient who received the drug was 92 years old.

Once upon a time, it took 10 years or even longer to develop and market an antibody drug, but the entire process of developing the anti-COVID-19 antibody drug by Zhang Linqi and his team took only 18 months.

The battle between humans and the epidemic

The third winter is coming

The world for

Demand for effective drugs against COVID-19

More and more urgent

Professor Zhang Linqi said:

"This is a nano-scale 'confrontation' between humans and viruses.

It has no smoke, and it will win in the end."

Salute to scientific researchers!

China Youth Daily (ID: zqbcyol) Compiled by Chen Yinshan) from the official microblog of Tsinghua University