Cargando…

Furin: A Potential Therapeutic Target for COVID-19

COVID-19 broke out in the end of December 2019 and is still spreading rapidly, which has been listed as an international concerning public health emergency. We found that the Spike protein of SARS-CoV-2 contains a furin cleavage site, which did not exist in any other betacoronavirus subtype B. Based...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Canrong, Zheng, Mengzhu, Yang, Yueying, Gu, Xiaoxia, Yang, Kaiyin, Li, Mingxue, Liu, Yang, Zhang, Qingzhe, Zhang, Peng, Wang, Yali, Wang, Qiqi, Xu, Yang, Zhou, Yirong, Zhang, Yonghui, Chen, Lixia, Li, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534598/
https://www.ncbi.nlm.nih.gov/pubmed/33043282
http://dx.doi.org/10.1016/j.isci.2020.101642
_version_ 1783590340951801856
author Wu, Canrong
Zheng, Mengzhu
Yang, Yueying
Gu, Xiaoxia
Yang, Kaiyin
Li, Mingxue
Liu, Yang
Zhang, Qingzhe
Zhang, Peng
Wang, Yali
Wang, Qiqi
Xu, Yang
Zhou, Yirong
Zhang, Yonghui
Chen, Lixia
Li, Hua
author_facet Wu, Canrong
Zheng, Mengzhu
Yang, Yueying
Gu, Xiaoxia
Yang, Kaiyin
Li, Mingxue
Liu, Yang
Zhang, Qingzhe
Zhang, Peng
Wang, Yali
Wang, Qiqi
Xu, Yang
Zhou, Yirong
Zhang, Yonghui
Chen, Lixia
Li, Hua
author_sort Wu, Canrong
collection PubMed
description COVID-19 broke out in the end of December 2019 and is still spreading rapidly, which has been listed as an international concerning public health emergency. We found that the Spike protein of SARS-CoV-2 contains a furin cleavage site, which did not exist in any other betacoronavirus subtype B. Based on a series of analysis, we speculate that the presence of a redundant furin cut site in its Spike protein is responsible for SARS-CoV-2's stronger infectious nature than other coronaviruses, which leads to higher membrane fusion efficiency. Subsequently, a library of 4,000 compounds including approved drugs and natural products was screened against furin through structure-based virtual screening and then assayed for their inhibitory effects on furin activity. Among them, an anti-parasitic drug, diminazene, showed the highest inhibition effects on furin with an IC(50) of 5.42 ± 0.11 μM, which might be used for the treatment of COVID-19.
format Online
Article
Text
id pubmed-7534598
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-75345982020-10-06 Furin: A Potential Therapeutic Target for COVID-19 Wu, Canrong Zheng, Mengzhu Yang, Yueying Gu, Xiaoxia Yang, Kaiyin Li, Mingxue Liu, Yang Zhang, Qingzhe Zhang, Peng Wang, Yali Wang, Qiqi Xu, Yang Zhou, Yirong Zhang, Yonghui Chen, Lixia Li, Hua iScience Article COVID-19 broke out in the end of December 2019 and is still spreading rapidly, which has been listed as an international concerning public health emergency. We found that the Spike protein of SARS-CoV-2 contains a furin cleavage site, which did not exist in any other betacoronavirus subtype B. Based on a series of analysis, we speculate that the presence of a redundant furin cut site in its Spike protein is responsible for SARS-CoV-2's stronger infectious nature than other coronaviruses, which leads to higher membrane fusion efficiency. Subsequently, a library of 4,000 compounds including approved drugs and natural products was screened against furin through structure-based virtual screening and then assayed for their inhibitory effects on furin activity. Among them, an anti-parasitic drug, diminazene, showed the highest inhibition effects on furin with an IC(50) of 5.42 ± 0.11 μM, which might be used for the treatment of COVID-19. Elsevier 2020-10-05 /pmc/articles/PMC7534598/ /pubmed/33043282 http://dx.doi.org/10.1016/j.isci.2020.101642 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Canrong
Zheng, Mengzhu
Yang, Yueying
Gu, Xiaoxia
Yang, Kaiyin
Li, Mingxue
Liu, Yang
Zhang, Qingzhe
Zhang, Peng
Wang, Yali
Wang, Qiqi
Xu, Yang
Zhou, Yirong
Zhang, Yonghui
Chen, Lixia
Li, Hua
Furin: A Potential Therapeutic Target for COVID-19
title Furin: A Potential Therapeutic Target for COVID-19
title_full Furin: A Potential Therapeutic Target for COVID-19
title_fullStr Furin: A Potential Therapeutic Target for COVID-19
title_full_unstemmed Furin: A Potential Therapeutic Target for COVID-19
title_short Furin: A Potential Therapeutic Target for COVID-19
title_sort furin: a potential therapeutic target for covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534598/
https://www.ncbi.nlm.nih.gov/pubmed/33043282
http://dx.doi.org/10.1016/j.isci.2020.101642
work_keys_str_mv AT wucanrong furinapotentialtherapeutictargetforcovid19
AT zhengmengzhu furinapotentialtherapeutictargetforcovid19
AT yangyueying furinapotentialtherapeutictargetforcovid19
AT guxiaoxia furinapotentialtherapeutictargetforcovid19
AT yangkaiyin furinapotentialtherapeutictargetforcovid19
AT limingxue furinapotentialtherapeutictargetforcovid19
AT liuyang furinapotentialtherapeutictargetforcovid19
AT zhangqingzhe furinapotentialtherapeutictargetforcovid19
AT zhangpeng furinapotentialtherapeutictargetforcovid19
AT wangyali furinapotentialtherapeutictargetforcovid19
AT wangqiqi furinapotentialtherapeutictargetforcovid19
AT xuyang furinapotentialtherapeutictargetforcovid19
AT zhouyirong furinapotentialtherapeutictargetforcovid19
AT zhangyonghui furinapotentialtherapeutictargetforcovid19
AT chenlixia furinapotentialtherapeutictargetforcovid19
AT lihua furinapotentialtherapeutictargetforcovid19