PT  - JOURNAL ARTICLE
AU  - Jiang, Liwei
AU  - Wang, Nianshuang
AU  - Zuo, Teng
AU  - Shi, Xuanling
AU  - Poon, Kwok-Man Vincent
AU  - Wu, Yongkang
AU  - Gao, Fei
AU  - Li, Danyang
AU  - Wang, Ruoke
AU  - Guo, Jianying
AU  - Fu, Lili
AU  - Yuen, Kwok-Yung
AU  - Zheng, Bo-Jian
AU  - Wang, Xinquan
AU  - Zhang, Linqi
TI  - Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein
AID  - 10.1126/scitranslmed.3008140
DP  - 2014 Apr 30
TA  - Science Translational Medicine
PG  - 234ra59--234ra59
VI  - 6
IP  - 234
4099  - http://stm.sciencemag.org/content/6/234/234ra59.short
4100  - http://stm.sciencemag.org/content/6/234/234ra59.full
AB  - The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection.