Institution: | a Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China b Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025, China c Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA d Beijing Institute of Basic Medical Sciences, Beijing 100850, China e Chinese National Human Genome Center at Shanghai, Shanghai 201203, China f Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China g Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA h Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China i The University of Hong Kong, Hong Kong j E-institutes of Shanghai Universities Immunology Division, Shanghai, China |
Abstract: | The receptor-binding domain (RBD) on spike protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the main region interacting with the viral receptor-ACE2 and is a useful target for induction of neutralizing antibodies against SARS-CoV infection. Here we generated two monoclonal antibodies (mAbs), targeting RBD, with marked virus neutralizing activity. The mAbs recognize a new conformational epitope which consists of several discontinuous peptides (aa. 343-367, 373-390 and 411-428) and is spatially located neighboring the receptor-binding motif (RPM) region of the RBD. Importantly, W423 and N424 residues are essential for mAb recognition and are highly conserved among 107 different strains of SARS, indicating that the residues are the most critical in the epitope which is a novel potential target for therapeutic mAbs. A human-mouse chimeric antibody, based upon the original murine mAb, was also constructed and shown to possess good neutralizing activity and high affinity. |