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A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein.
J Virol. 2014 Jun; 88(12):7045-53.JV

Abstract

Prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have developed a neutralizing monoclonal antibody (MAb), designated Mersmab1, which potently blocks MERS-CoV entry into human cells. Biochemical assays reveal that Mersmab1 specifically binds to the receptor-binding domain (RBD) of the MERS-CoV spike protein and thereby competitively blocks the binding of the RBD to its cellular receptor, dipeptidyl peptidase 4 (DPP4). Furthermore, alanine scanning of the RBD has identified several residues at the DPP4-binding surface that serve as neutralizing epitopes for Mersmab1. These results suggest that if humanized, Mersmab1 could potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies of the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines.

IMPORTANCE

MERS-CoV is spreading in the human population and causing severe respiratory diseases with over 40% fatality. No vaccine is currently available to prevent MERS-CoV infections. Here, we have produced a neutralizing monoclonal antibody with the capacity to effectively block MERS-CoV entry into permissive human cells. If humanized, this antibody may be used as a prophylactic and therapeutic agent against MERS-CoV infections. Specifically, when given to a person (e.g., a patient's family member or a health care worker) either before or after exposure to MERS-CoV, the humanized antibody may prevent or inhibit MERS-CoV infection, thereby stopping the spread of MERS-CoV in humans. This antibody can also serve as a useful tool to guide the design of effective MERS-CoV vaccines.

Authors+Show Affiliations

Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Department of Microbiology and Immunology, and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas, USA.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Department of Microbiology and Immunology, and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas, USA.Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China.Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA lifang@umn.edu yszhou@bmi.ac.cn.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China lifang@umn.edu yszhou@bmi.ac.cn.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24719424

Citation

Du, Lanying, et al. "A Conformation-dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein." Journal of Virology, vol. 88, no. 12, 2014, pp. 7045-53.
Du L, Zhao G, Yang Y, et al. A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein. J Virol. 2014;88(12):7045-53.
Du, L., Zhao, G., Yang, Y., Qiu, H., Wang, L., Kou, Z., Tao, X., Yu, H., Sun, S., Tseng, C. T., Jiang, S., Li, F., & Zhou, Y. (2014). A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein. Journal of Virology, 88(12), 7045-53. https://doi.org/10.1128/JVI.00433-14
Du L, et al. A Conformation-dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein. J Virol. 2014;88(12):7045-53. PubMed PMID: 24719424.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein. AU - Du,Lanying, AU - Zhao,Guangyu, AU - Yang,Yang, AU - Qiu,Hongjie, AU - Wang,Lili, AU - Kou,Zhihua, AU - Tao,Xinrong, AU - Yu,Hong, AU - Sun,Shihui, AU - Tseng,Chien-Te K, AU - Jiang,Shibo, AU - Li,Fang, AU - Zhou,Yusen, Y1 - 2014/04/09/ PY - 2014/4/11/entrez PY - 2014/4/11/pubmed PY - 2014/10/1/medline SP - 7045 EP - 53 JF - Journal of virology JO - J Virol VL - 88 IS - 12 N2 - UNLABELLED: Prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have developed a neutralizing monoclonal antibody (MAb), designated Mersmab1, which potently blocks MERS-CoV entry into human cells. Biochemical assays reveal that Mersmab1 specifically binds to the receptor-binding domain (RBD) of the MERS-CoV spike protein and thereby competitively blocks the binding of the RBD to its cellular receptor, dipeptidyl peptidase 4 (DPP4). Furthermore, alanine scanning of the RBD has identified several residues at the DPP4-binding surface that serve as neutralizing epitopes for Mersmab1. These results suggest that if humanized, Mersmab1 could potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies of the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines. IMPORTANCE: MERS-CoV is spreading in the human population and causing severe respiratory diseases with over 40% fatality. No vaccine is currently available to prevent MERS-CoV infections. Here, we have produced a neutralizing monoclonal antibody with the capacity to effectively block MERS-CoV entry into permissive human cells. If humanized, this antibody may be used as a prophylactic and therapeutic agent against MERS-CoV infections. Specifically, when given to a person (e.g., a patient's family member or a health care worker) either before or after exposure to MERS-CoV, the humanized antibody may prevent or inhibit MERS-CoV infection, thereby stopping the spread of MERS-CoV in humans. This antibody can also serve as a useful tool to guide the design of effective MERS-CoV vaccines. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/24719424/A_conformation_dependent_neutralizing_monoclonal_antibody_specifically_targeting_receptor_binding_domain_in_Middle_East_respiratory_syndrome_coronavirus_spike_protein_ L2 - https://journals.asm.org/doi/10.1128/JVI.00433-14?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -