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.