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Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory illness with fever, cough and shortness of breath. Up to date, it has resulted in 1826 human infections, including 649 deaths. Analogous to picornavirus 3C protease (3C(pro)), 3C-like protease (3CL(pro)) is criti...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113684/ https://www.ncbi.nlm.nih.gov/pubmed/28216367 http://dx.doi.org/10.1016/j.antiviral.2017.02.007 |
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author | Kumar, Vathan Shin, Jin Soo Shie, Jiun-Jie Ku, Keun Bon Kim, Chonsaeng Go, Yun Young Huang, Kai-Fa Kim, Meehyein Liang, Po-Huang |
author_facet | Kumar, Vathan Shin, Jin Soo Shie, Jiun-Jie Ku, Keun Bon Kim, Chonsaeng Go, Yun Young Huang, Kai-Fa Kim, Meehyein Liang, Po-Huang |
author_sort | Kumar, Vathan |
collection | PubMed |
description | Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory illness with fever, cough and shortness of breath. Up to date, it has resulted in 1826 human infections, including 649 deaths. Analogous to picornavirus 3C protease (3C(pro)), 3C-like protease (3CL(pro)) is critical for initiation of the MERS-CoV replication cycle and is thus regarded as a validated drug target. As presented here, our peptidomimetic inhibitors of enterovirus 3C(pro) (6b, 6c and 6d) inhibited 3CL(pro) of MERS-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV) with IC(50) values ranging from 1.7 to 4.7 μM and from 0.2 to 0.7 μM, respectively. In MERS-CoV-infected cells, the inhibitors showed antiviral activity with EC(50) values ranging from 0.6 to 1.4 μM, by downregulating the viral protein production in cells as well as reducing secretion of infectious viral particles into culture supernatants. They also suppressed other α- and β-CoVs from human and feline origin. These compounds exhibited good selectivity index (over 70 against MERS-CoV) and could lead to the development of broad-spectrum antiviral drugs against emerging CoVs and picornaviruses. |
format | Online Article Text |
id | pubmed-7113684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71136842020-04-02 Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors Kumar, Vathan Shin, Jin Soo Shie, Jiun-Jie Ku, Keun Bon Kim, Chonsaeng Go, Yun Young Huang, Kai-Fa Kim, Meehyein Liang, Po-Huang Antiviral Res Article Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory illness with fever, cough and shortness of breath. Up to date, it has resulted in 1826 human infections, including 649 deaths. Analogous to picornavirus 3C protease (3C(pro)), 3C-like protease (3CL(pro)) is critical for initiation of the MERS-CoV replication cycle and is thus regarded as a validated drug target. As presented here, our peptidomimetic inhibitors of enterovirus 3C(pro) (6b, 6c and 6d) inhibited 3CL(pro) of MERS-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV) with IC(50) values ranging from 1.7 to 4.7 μM and from 0.2 to 0.7 μM, respectively. In MERS-CoV-infected cells, the inhibitors showed antiviral activity with EC(50) values ranging from 0.6 to 1.4 μM, by downregulating the viral protein production in cells as well as reducing secretion of infectious viral particles into culture supernatants. They also suppressed other α- and β-CoVs from human and feline origin. These compounds exhibited good selectivity index (over 70 against MERS-CoV) and could lead to the development of broad-spectrum antiviral drugs against emerging CoVs and picornaviruses. Elsevier B.V. 2017-05 2017-02-17 /pmc/articles/PMC7113684/ /pubmed/28216367 http://dx.doi.org/10.1016/j.antiviral.2017.02.007 Text en © 2017 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Kumar, Vathan Shin, Jin Soo Shie, Jiun-Jie Ku, Keun Bon Kim, Chonsaeng Go, Yun Young Huang, Kai-Fa Kim, Meehyein Liang, Po-Huang Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors |
title | Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors |
title_full | Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors |
title_fullStr | Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors |
title_full_unstemmed | Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors |
title_short | Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors |
title_sort | identification and evaluation of potent middle east respiratory syndrome coronavirus (mers-cov) 3cl(pro) inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113684/ https://www.ncbi.nlm.nih.gov/pubmed/28216367 http://dx.doi.org/10.1016/j.antiviral.2017.02.007 |
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