Chinese scientists structurally reveal that BD-368-2 antibody can effectively treat hamsters severely infected by the new coronavirus

  Understanding how effective neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is the key to developing effective therapies. In a previous new study, using the expertise of single-cell genomics, Peking University Beijing Advanced Innovation Center for Future Genetic Diagnosis Xie Xiaoliang’s team conducted a study on the deputy dean of Beijing You’an Hospital affiliated to Capital Medical University. Blood samples were collected from more than 60 convalescent patients. In these blood samples, 14 highly effective neutralizing antibodies were screened from 8558 antigen-binding IgG1 + timing types. As the most effective antibody, BD-368-2 has IC50 values of 8pM and 100pM for SARS-CoV-2 pseudovirus and actual SARS-CoV-2 virus, respectively.

  These researchers used the hACE2 transgenic mouse model developed by the laboratory of Dr. Hatakawa of the Institute of Experimental Animals of the Chinese Academy of Medical Sciences to complete the in vivo antiviral experiments of neutralizing antibodies. .. Experimental results show that BD-368-2 antibody has a strong therapeutic and preventive effect on SARS-CoV-2. Injection of BD-368-2 antibody into infected mice can reduce viral load by approximately 5%. 2400 times; injection of BD-368-2 antibody into uninfected mice can prevent virus infection. However, little is known about the mechanism by which BD-368-2 antibody neutralizes SARS-CoV-2. Therefore, in a new study, these researchers reported the use of BD-368-2 in combination with the SARS-CoV-2 spike protein (S protein) trimer complex with a resolution of 3.5 angstroms. The cryo-EM structure ensures that BD-368-2 completely prevents the S protein trimer complex from recognizing ACE2 by simultaneously occupying all three receptor binding domains (RBD) regardless of RBD.

  is true for both "top" and "bottom" conformations. In addition, BD-368-2 can treat infected adult hamsters at low doses during different administration periods, while infected hamsters treated with placebo showed severe interstitial pneumonia. In addition, the BD-368-2 epitope completely avoids the repeated common binding sites of the VH3-53/VH3-66 neutralizing antibody. The tripartite eutectic structure with RBD also confirms this. Repeated pairing of BD-368-2 and strong neutralizing antibody can neutralize SARS-CoV-2 pseudovirus at the pM level and preserve the neutralization escape caused by mutation. All in all, these researchers rationally designed new RBD epitopes that can lead to high school students and curative effects, and confirmed the potential of using BD-368-2 in the treatment of COVID-19.