Chinese scientists have successfully developed a broad-spectrum humanized genetically engineered monoclonal antibody against the new coronavirus pneumonia virus

On August 17, Yan Jinghua’s team from the Institute of Microbiology , Chinese Academy of Sciences joined Huazhong University of Science and Technology Wang Chenhui’s team, Peking University Xiao Junyu’s team, China Food and Drug Control Research Institute Wang Youchun team, China Centers for Disease Control and Prevention Tan Wenjie team, Shanghai Junshi Biomedical Technology Co.

This paper reports for the first time a blocking antibody that targets multiple coronavirus invasion receptors ACE2; this antibody can effectively prevent and treat the novel coronavirus (SARS-CoV-2) and its mutants from infecting host cells and model animals , And shows good safety in non-human primates

The researchers first obtained a blocking monoclonal antibody h11B11 that targets the human ACE2 receptor through rapid screening and humanization of the antibody; the neutralization evaluation of pseudoviruses and true viruses of a variety of coronaviruses confirmed that the antibody h11B11 It has good inhibitory activity against SARS-CoV, SARS-CoV-2 and its mutant viruses; the combination of this antibody and the new crown therapeutic antibody CB6 developed by the Institute of Microbiology in the early stage can synergistically increase the neutralizing activity

CB6 monoclonal antibody is an antibody that targets the S protein RBD of the new crown pneumonia virus.

Figure 1.

The researchers conducted further in vivo activity evaluation of the antibody through the SARS-CoV-2 model of hACE2 transgenic mice.

Figure 2.

Since the ACE2 receptor can maintain the balance of blood pressure in the body, the binding of the antibody h11B11 to the ACE2 receptor may affect its physiological functions

The researchers used the cynomolgus monkey model to evaluate the preclinical safety of the h11B11 antibody.

The results showed that even if the cynomolgus monkeys were given high-dose h11B11 antibody three times, their blood pressure and blood chemical toxicological indicators did not change significantly, proving that the antibody has good in vivo safety (Figure 3)

Figure 3.

To clarify the mechanism of action and the binding epitope h11B11 antibodies, researchers further resolved crystal structure h11B11 and ACE2; and the structure shows that the anti- body mainly bound α-helical domain ACE2 receptor N-terminus; the antibody by epitope competition and space The steric hindrance effect blocks the binding of the SARS-CoV and SARS-CoV-2 RBD regions to the ACE2 receptor to inhibit the virus from invading host cells (Figure 4)

Figure 4.

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