The results of scientific publishing Gao Fu and other research found two obstacles

The team of scientists from China found that two monoclonal antibodies B38 and H4 antibodies separated from a rehabilitation of crown disease can prevent the combination of viral S protein receptor combined with regional RBD and human cell receptor2.Subsequent treatment in mouse models confirmed that these two antibodies can reduce the virus load in the lungs after mice infection.

According to the surging news report, on May 13th local time, the top academic journal science (Science) online published the key laboratory of pathogenesis and immunology of the Chinese Academy of Sciences, the Institute of Microbiology of the Chinese Academy of Sciences,A research of a research jointly completed by the Chinese University of Science and Technology, Shenzhen Third People's Hospital, China Agricultural University, the Tianjin Institute of Industrial Technology of the Chinese Academy of Sciences, and the China Disease Prevention and Control Center.TO ITS Receptor ACE2 (a pair of non-competitive humans neutralized antibodies can block the combination of COVID-19 virus and its receptor ACE2), and disclose the above research results.

The author of the study was Gao Fook, Director of the China Centers for Disease Control and Prevention, academician of the Chinese Academy of Sciences, Gao Feng, an associate researcher at the Tianjin Institute of Industrial Biotechnology of the Chinese Academy of Sciences, and Liu Lei, dean of Shenzhen Third People's Hospital.The study had previously been published on May 7, local time, and published on the biological pre -printed website MEDRXIV.

The research team is separated from four human -source monoclonal antibodies from a Chinese rehabilitation patient, which shows neutrality in vitro. Among them, the B38 and H4 antibodies are particularly potential.

So far, the coronary virus has no specific drugs or vaccines.At present, most of the treatment R & D programs are aimed at the key to the new coronal virus to invade humans mdash; mdash; S protein (spiny glycoprotein).S protein -mediated virus and host cells combined and invaded. It consists of two parts: S1 domain and S2 domain, which respectively mediate receptor binding and membrane fusion, respectively. The receptor binding domain (RBD) is S1.The research team believes that the neutral and antibodies that use RBD protein to screen the coronary virus are priority strategies that can be adopted at the moment.

They first obtained four different antibodies (B5, B38, H2, and H4) from patients with new crown recovery periods. Its clear liquid shows that it can be combined with the new crown virus RBD, but the combination of the RBD of SARS-COV failed, which indicates that SARS-COVThe RBD surface of the coronary virus is different in immunology.

These four antibodies show the different combination of RBD with the coronary virus, and the KD range of 10 to 10 is 10 to 10.Among them, H4 shows a relatively high binding affinity. The KD is 4.48nm, while the B5 shows a relatively weak binding affinity. The KD is 305nm.B38 and H2 are combined with RBD, and KDs are 70.1nm and 14.3nm, respectively.

All four antibodies are neutralized, and the range of IC50 (semi -inhibitory concentration) is 0.177mu; G/ML to 1.375mu; g/ml.B38 is the most effective antibody, followed by H4, H2 and B5.

The research team will then evaluate the competitiveness of each antibody to block the combination of virus RBD and ACE2. The results show that B38 and H4 can fully compete with ACE2 and combine with RBD.Instead, the B5 shows some competition, while H2 shows a combination with RBD, but does not compete with ACE2.

Studies also show that B38 and H4 can identify different tables on RBD and partially overlap.

Studies have pointed out that competition analysis shows that the different tables of these two antibodies on RBD make them a potential virus -targeted monoclonal antibody pair to avoid immune escape from clinical application in the future.

In order to explore the protection effects of B38 and H4's anti -new coronal virus attack in the body, the research team conducted mouse treatment experiments.After 12 hours of attack, the research team injected 25 mg/kg single -dose B38 or H4 into the HACE2 transgenic mice.The results showed that compared with the control group and H4 group, the B38 group of mice with a significant decrease in weight after attack recovered 3 days after infection (DPI).

The research team also detected the virus RNA copy of the mouse lung tissue during 3 DPI.The relative RNA copies of the B38 and H4 groups were significantly lower than the control group, and the control group was reduced by 32.8 % and 26 % respectively compared with the control group.

In order to further clarify the structural foundation of the antibody neutralization mechanism, the research team prepared RBD-B38 and RBD-H4 FAB complex through in vitro incubation and purification.The three complementary decision zones (CDRS) and the two complementary decisive zones on the light chain participation and the role of virus RBD.There are 36 residues in the virus RBD that interact with the B38, of which 21 residues are interacted with heavy chain, and 15 residues are interacted with light chain.

The sequence comparison indicates that among the 36 residues in the table, only 15 are conservative between coronary virus and SARS-COV.This explains the specific response of B38.

The team also studied the structural basis of B38 blocking Covid-19 virus RBD and ACE2.The results showed that the VH and VLs of B38 both led to spatial resistance combined with RBD and ACE2.It is worth noting that in the two forms that are combined with the B38 and the HACE2, the RBD has not showed obvious structural changes.Further analysis found that when combined with the two, 18 of the 21 amino acids on RBD were completely consistent, which clearly explained why the B38 completely eliminates the combination of coronal virus RBD and receptor.

Studies emphasize that with the continuous spread of the new crown epidemic, the appraisal of the virus RBD protein table is essential, which will provide valuable information for the development of vaccine.In addition, the molecular characteristics of neutralized antibodies in the surface help the development of small molecules or peptide drugs/inhibitors.

In summary, the study believes that the neutral antibody of this study and identification is expected to become a candidate antibody to prevent and treat coronary virus.