RT Journal Article
SR Electronic
T1 Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 234ra59
OP 234ra59
DO 10.1126/scitranslmed.3008140
VO 6
IS 234
A1 Jiang, Liwei
A1 Wang, Nianshuang
A1 Zuo, Teng
A1 Shi, Xuanling
A1 Poon, Kwok-Man Vincent
A1 Wu, Yongkang
A1 Gao, Fei
A1 Li, Danyang
A1 Wang, Ruoke
A1 Guo, Jianying
A1 Fu, Lili
A1 Yuen, Kwok-Yung
A1 Zheng, Bo-Jian
A1 Wang, Xinquan
A1 Zhang, Linqi
YR 2014
UL http://stm.sciencemag.org/content/6/234/234ra59.abstract
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.