Conserved amino acids W423 and N424 in receptor-binding domain of SARS-CoV are potential targets for therapeutic monoclonal antibody

被引：13

作者：

Bian, Chao ^{[1
]}

Zhang, Xiuqin ^{[1
]}

Cai, Xingfeng ^{[1
]}

Zhang, Linqi ^{[3
]}

Chen, Zhiwei ^{[3
]}

Zha, Ye ^{[1
]}

Xu, Ying ^{[1
]}

Xu, Ke ^{[1
]}

Lu, Wei ^{[1
]}

Yan, Linchen ^{[1
]}

Yuan, Jianwei ^{[1
]}

Feng, Jiannan ^{[4
]}

Hao, Pei ^{[5
]}

Wang, Qidi ^{[6
,7
]}

Zhao, Guoping ^{[5
]}

Liu, Gang ^{[6
,7
]}

Zhu, Xueliang ^{[1
]}

Shen, Hao ^{[8
,9
]}

Zheng, Bojian ^{[10
]}

Shen, Beifen ^{[4
]}

Sun, Bing ^{[1
,2
,11
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yueyang Rd, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Inst Pasteur Shanghai, Shanghai 200025, Peoples R China

[3] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA

[4] Beijing Inst Basic Med Sci, Beijing 100850, Peoples R China

[5] Chinese Natl Human Genome Ctr Shanghai, Shanghai 201203, Peoples R China

[6] Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China

[7] Peking Union Med Coll, Beijing 100050, Peoples R China

[8] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[9] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Hosp, Shanghai Inst Med Genet, Shanghai 200040, Peoples R China

[10] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China

[11] Shanghai Univ E Inst, Div Immunol, Shanghai, Peoples R China

来源：

VIROLOGY | 2009年 / 383卷 / 01期

基金：

中国国家自然科学基金;

关键词：

SARS-CoV; Receptor-binding domain; Neutralization; Monoclonal antibody; Epitope; Chimeric; ACUTE RESPIRATORY SYNDROME; ANGIOTENSIN-CONVERTING ENZYME-2; CORONAVIRUS-S-PROTEIN; SPIKE PROTEIN; NEUTRALIZING ANTIBODIES; VIRUS; GLYCOPROTEIN; VACCINE; ENTRY; 80R;

D O I：

10.1016/j.virol.2008.09.029

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：39 / 46

页数：8

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