Conserved amino acids W423 and N424 in receptor-binding domain of SARS-CoV are potential targets for therapeutic monoclonal antibody.
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.
Bian
Chao
C
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.
Zhang
Xiuqin
X
Cai
Xingfeng
X
Zhang
Linqi
L
Chen
Zhiwei
Z
Zha
Ye
Y
Xu
Ying
Y
Xu
Ke
K
Lu
Wei
W
Yan
Linchen
L
Yuan
Jianwei
J
Feng
Jiannan
J
Hao
Pei
P
Wang
Qidi
Q
Zhao
Guoping
G
Liu
Gang
G
Zhu
Xueliang
X
Shen
Hao
H
Zheng
Bojian
B
Shen
Beifen
B
Sun
Bing
B
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
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins