(Correspondent Du Yanyun) on August 18, Professor Wang Chenhui’ team in Huazhong University of science and technology together with Institute of Microbiology, Chinese Academy of Sciences, Peking University, China Institute of food and drug control and The Chinese Center for Disease Control and Prevention published a research paper entitled "a widely neutralizing humanized ace2-targeting antibody against SARS-CoV-2 variants" in the international authoritative journal Nature communications.
At present, COVID-19 has infected more than two hundred million people worldwide, and caused more than 4 million 300 thousand deaths. In addition, many COVID-19 mutants have been raging around the world. Previously reports found that the Delta strain of the SARS-CoV-2 virus has spread to 92 countries. Due to the remarkable enhancement of the transmission ability of the delta mutant strain, the mutant COVID-19 is becoming the world's major popular variant of COVID-19. Therefore, it is urgent to develop special drug blocking drugs targeting different mutants of COVID-19.
A team of Professor Wang Chenhui of Huazhong University of Science and Technology jointly collaborated many research institutes in China, including the Institute of Microbiology of Chinese Academy of Sciences, Peking University, and developed a humanized antibody inhibitor 11B11 targeting COVID-19 receptor ACE2. The antibody inhibitor can not only block the infection cells of COVID-19 original strain, but also block the infection cells of various COVID-19 mutant strains. In addition, the antibody inhibitor can block the infection of COVID-19 (SARS-CoV) that were prevalent in 2003.
In addition, the antibody inhibitor did not affect the enzyme activity of ACE2, suggesting its safety in vivo.Through the virus attack experiment in mice, it was found that injection of 11B11 could significantly inhibit the viral load in the lungs and reduce the state and injury of pneumonia in mice. It should be noted that 11B11 (pre-exposure) was injected the day before the virus infection, and the virus could hardly be detected in the lung tissue of mice five days later; 11B11 (post-exposure) was injected one day after infection, and the viral load in mouse lung decreased 10 folds five days after infection.
The preliminary safety evaluation test found that even at the high dose (180mg / kg), no obvious blood pressure fluctuation and liver and blood biochemical abnormalities were found in cynomolgus monkeys, suggesting that the antibody inhibitor has good safety in vivo.
Through structural analysis, it was found that the affinity of 11B11 and ACE2 was about 45 times higher than that of SARS-CoV-2 and ACE2, which is the molecular basis of 11B11 blocking COVID-19 infection.
Collectively, the antibody inhibitors for ACE2 have the following advantages: 1) broad-spectrum: not only can block COVID-19 infection, but also block many coronavirus which through ACE2 as a receptor; 2) universality: a variety of COVID-19 mutant strains were blocked; 3) Safety: the preliminary safety evaluation shows that it has good safety. At present, the antibody inhibitor and other candidate antibody inhibitors against ACE2 are in various preparations before clinical trials, and are expected to go into clinical practice and save lifes.
Du Yanyun, a doctoral student from the school of life, Huazhong University of science and technology, Shi Rui, an assistant researcher at the Institute of Microbiology, Chinese Academy of Sciences, and Zhang Ying, a doctoral student from Peking University, were the co-first authors of the paper. Huazhong University of science and technology is the first unit of the paper. Yan Jinghua, researcher of Institute of Microbiology, Chinese Academy of Sciences, Wang Chenhui, Professor of School of life, Huazhong University of science and technology, Wang Youchun, researcher of China Institute of food and drug control, and Tan Wenjie, researcher of China Center for Disease Control and prevention are the co-corresponding authors of this article. This work was supported by the Strategic Priority Research Program of CAS (XDB29040201), National Natural Science Foundation of China (81830050 and 81871280), the Junior Thousand Talents Program of China (to C.W.), and the Emergency Grant for COVID-19 of Huazhong University of Science and Technology (2020kfyXGYJ110).
