A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Corresponding authors: Yan Wu, Feng Gao, George Fu Gao, Lei Liu

Affiliations: Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People’s Hospital, Shenzhen, China; College of Veterinary Medicine, China Agricultural University, Beijing, China; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences (CAS), Tianjin, China; Shanxi Academy of Advanced Research and Innovation, Taiyuan, China; University of Chinese Academy of Sciences, Beijing, China; Center for Influenza Research and Early Warning, Chinese Academy of Sciences (CASCIRE), Beijing, China; NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Laboratory Animal Center, Chinese Center for Disease Control and Prevention, Beijing, China; Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, China

Publication date: this article was published online on June 12, 2020

DOI: 10.1126/science.abc2241

Highlights

In this article, the authors report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on the RBD for these two antibodies, making them a potentially promising virus-targeting monoclonal antibody pair for avoiding immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity.

Nomination Reasons

As the COVID-19 outbreak continues to spread, characterization of the epitopes on SARS-CoV-2 RBD will provide valuable information for vaccine development. Furthermore, the molecular features of the neutralizing antibody targeting epitopes are helpful for the development of small-molecule or peptide drugs and inhibitors. The neutralizing antibodies themselves are also promising candidates for prophylactic and therapeutic treatment against SARS-CoV-2.

----------------------------------------------------------------------------------------------------------------------------------------------

This article has been nominated for Distinguished Research Awards, you can visit the website below and vote for the nominated publications:

https://www.molecularcloud.org/awards-for-distinguished-research.html.