title: Conserved amino acids W423 and N424 in receptor-binding domain of SARS-CoV are potential targets for therapeutic monoclonal antibody.
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.
authors.affiliation: 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Bian
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Zhang
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Cai
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Zha
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Linchen
authors.initials: L
authors.lastname: Yan
authors.forename: Jianwei
authors.initials: J
authors.lastname: Yuan
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.forename: Pei
authors.initials: P
authors.lastname: Hao
authors.forename: Qidi
authors.initials: Q
authors.lastname: Wang
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Xueliang
authors.initials: X
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Bojian
authors.initials: B
authors.lastname: Zheng
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D017124:Conserved Sequence / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology / Q000502:physiology*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D053585:Virus Attachment
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins