Biomaterial Database

Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. 2014

Liwei Jiang, and Nianshuang Wang, and Teng Zuo, and Xuanling Shi, and Kwok-Man Vincent Poon, and Yongkang Wu, and Fei Gao, and Danyang Li, and Ruoke Wang, and Jianying Guo, and Lili Fu, and Kwok-Yung Yuen, and Bo-Jian Zheng, and Xinquan Wang, and Linqi Zhang

Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.

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.

UI	MeSH Term	Description	Entries
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000914	Antibodies, Viral	Immunoglobulins produced in response to VIRAL ANTIGENS.	Viral Antibodies
D057134	Antibodies, Neutralizing	Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.	Neutralizing Antibodies,Antibody, Neutralizing,Neutralizing Antibody
D020128	Inhibitory Concentration 50	The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.	IC50,Concentration 50, Inhibitory
D065207	Middle East Respiratory Syndrome Coronavirus	A coronavirus first reported in the summer of 2012 in a pneumonia patient in SAUDI ARABIA. It is related to SEVERE ACUTE RESPIRATORY SYNDROME-RELATED CORONAVIRUS. MERS-CoV has an estimated incubation period of 12 days and symptoms include renal failure and severe acute pneumonia with often fatal outcome.	Merbecovirus,MERS Virus,MERS-CoV,Middle East respiratory syndrome-related coronavirus,MERS Viruses,Merbecoviruses,Middle East respiratory syndrome related coronavirus,Virus, MERS