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Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-fi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618021/ https://www.ncbi.nlm.nih.gov/pubmed/28906430 http://dx.doi.org/10.3390/v9090255 |
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author | Sun, Yaping Zhang, Huaidong Shi, Jian Zhang, Zhe Gong, Rui |
author_facet | Sun, Yaping Zhang, Huaidong Shi, Jian Zhang, Zhe Gong, Rui |
author_sort | Sun, Yaping |
collection | PubMed |
description | The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (K(D)) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC(50)) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent. |
format | Online Article Text |
id | pubmed-5618021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-56180212017-09-29 Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus Sun, Yaping Zhang, Huaidong Shi, Jian Zhang, Zhe Gong, Rui Viruses Article The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (K(D)) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC(50)) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent. MDPI 2017-09-14 /pmc/articles/PMC5618021/ /pubmed/28906430 http://dx.doi.org/10.3390/v9090255 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sun, Yaping Zhang, Huaidong Shi, Jian Zhang, Zhe Gong, Rui Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus |
title | Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus |
title_full | Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus |
title_fullStr | Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus |
title_full_unstemmed | Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus |
title_short | Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus |
title_sort | identification of a novel inhibitor against middle east respiratory syndrome coronavirus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618021/ https://www.ncbi.nlm.nih.gov/pubmed/28906430 http://dx.doi.org/10.3390/v9090255 |
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