A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in middle east respiratory syndrome coronavirus spike protein

Lanying Du, Guangyu Zhao, Yang Yang, Hongjie Qiu, Lili Wang, Zhihua Kou, Xinrong Tao, Hong Yu, Shihui Sun, Chien-Te Tseng, Shibo Jiang, Fang Li, Yusen Zhou

Research output: Contribution to journalArticle

65 Citations (Scopus)

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 MERSCoV 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.

Original languageEnglish (US)
Pages (from-to)7045-7053
Number of pages9
JournalJournal of Virology
Volume88
Issue number12
DOIs
StatePublished - 2014

Fingerprint

Coronavirus Spike Glycoproteins
Neutralizing Antibodies
neutralizing antibodies
monoclonal antibodies
Monoclonal Antibodies
receptors
proteins
Coronavirus Infections
Dipeptidyl Peptidase 4
Antibodies, Monoclonal, Humanized
antibodies
infection
peptidases
Middle East Respiratory Syndrome Coronavirus
Middle East respiratory syndrome coronavirus
therapeutics
Vaccines
vaccines
Subunit Vaccines
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in middle east respiratory syndrome coronavirus spike protein. / Du, Lanying; Zhao, Guangyu; Yang, Yang; Qiu, Hongjie; Wang, Lili; Kou, Zhihua; Tao, Xinrong; Yu, Hong; Sun, Shihui; Tseng, Chien-Te; Jiang, Shibo; Li, Fang; Zhou, Yusen.

In: Journal of Virology, Vol. 88, No. 12, 2014, p. 7045-7053.

Research output: Contribution to journalArticle

Du, Lanying ; Zhao, Guangyu ; Yang, Yang ; Qiu, Hongjie ; Wang, Lili ; Kou, Zhihua ; Tao, Xinrong ; Yu, Hong ; Sun, Shihui ; Tseng, Chien-Te ; Jiang, Shibo ; Li, Fang ; Zhou, Yusen. / A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in middle east respiratory syndrome coronavirus spike protein. In: Journal of Virology. 2014 ; Vol. 88, No. 12. pp. 7045-7053.
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