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

详细信息    查看全文

• 作者：Chao Bian ; Xiuqin Zhang ; Xingfeng Cai ; Linqi Zhang ; Zhiwei Chen ; Ye Zha ; Ying Xu ; Ke Xu ; Wei Lu ; Linchen Yan ; Jianwei Yuan ; Jiannan Feng ; Pei Hao ; Qidi Wang ; Guoping Zhao ; Gang Liu ; Xueliang Zhu ; Hao
• 关键词：SARS-CoV ; Receptor-binding domain ; Neutralization ; Monoclonal antibody ; Epitope ; Chimeric
• 刊名：Virology
• 出版年：2009
• 出版时间：5 January 2009
• 年：2009
• 卷：383
• 期：1
• 页码：39-46
• 全文大小：452 K

文摘

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.