Giuseppe
Emeritus
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
Open Access / Peer-Reviewed
Research Article
A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines
Lanying Du, Zhihua Kou, Cuiqing Ma, Xinrong Tao, Lili Wang, Guangyu Zhao, Yaoqing Chen, Fei Yu, Chien-Te K. Tseng, Yusen Zhou, Shibo Jiang
Published: December 04, 2013 - DOI: 10.1371/journal.pone.0081587
Abstract
An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367?606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients? lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.
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Citation: Du L, Kou Z, Ma C, Tao X, Wang L, et al. (2013) A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines. PLoS ONE 8(12): e81587. doi:10.1371/journal.pone.0081587
Editor: Zhiwei Chen, The University of Hong Kong, Hong Kong
Received: September 28, 2013; Accepted: October 22, 2013; Published: December 4, 2013
Copyright: ? 2013 Du et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was supported by grants from the New York Blood Center (NYB000068) and the National 973 Program of China (2011CB504706, 2012CB519001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: Drs. Lanying Du and Shibo Jiang are PLOS ONE Editorial Board members. This does not alter the authors? adherence to all PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
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Open Access / Peer-Reviewed
Research Article
A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines
Lanying Du, Zhihua Kou, Cuiqing Ma, Xinrong Tao, Lili Wang, Guangyu Zhao, Yaoqing Chen, Fei Yu, Chien-Te K. Tseng, Yusen Zhou, Shibo Jiang
Published: December 04, 2013 - DOI: 10.1371/journal.pone.0081587
Abstract
An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367?606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients? lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.
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Citation: Du L, Kou Z, Ma C, Tao X, Wang L, et al. (2013) A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines. PLoS ONE 8(12): e81587. doi:10.1371/journal.pone.0081587
Editor: Zhiwei Chen, The University of Hong Kong, Hong Kong
Received: September 28, 2013; Accepted: October 22, 2013; Published: December 4, 2013
Copyright: ? 2013 Du et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was supported by grants from the New York Blood Center (NYB000068) and the National 973 Program of China (2011CB504706, 2012CB519001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: Drs. Lanying Du and Shibo Jiang are PLOS ONE Editorial Board members. This does not alter the authors? adherence to all PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
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