25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination o...

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Autores principales:	Qiaoshuai Lan, Chao Wang, Jie Zhou, Lijue Wang, Fanke Jiao, Yanbo Zhang, Yanxing Cai, Lu Lu, Shuai Xia, Shibo Jiang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	human coronavirus 25-Hydroxycholesterol fusion inhibitor lipopeptide Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/cce3f0137fe845309189e2abf1f1776f
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spelling	oai:doaj.org-article:cce3f0137fe845309189e2abf1f1776f2021-11-11T17:17:27Z25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses10.3390/ijms2221118691422-00671661-6596https://doaj.org/article/cce3f0137fe845309189e2abf1f1776f2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11869https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.Qiaoshuai LanChao WangJie ZhouLijue WangFanke JiaoYanbo ZhangYanxing CaiLu LuShuai XiaShibo JiangMDPI AGarticlehuman coronavirus25-Hydroxycholesterolfusion inhibitorlipopeptideBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11869, p 11869 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human coronavirus 25-Hydroxycholesterol fusion inhibitor lipopeptide Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	human coronavirus 25-Hydroxycholesterol fusion inhibitor lipopeptide Biology (General) QH301-705.5 Chemistry QD1-999 Qiaoshuai Lan Chao Wang Jie Zhou Lijue Wang Fanke Jiao Yanbo Zhang Yanxing Cai Lu Lu Shuai Xia Shibo Jiang 25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses
description	The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.
format	article
author	Qiaoshuai Lan Chao Wang Jie Zhou Lijue Wang Fanke Jiao Yanbo Zhang Yanxing Cai Lu Lu Shuai Xia Shibo Jiang
author_facet	Qiaoshuai Lan Chao Wang Jie Zhou Lijue Wang Fanke Jiao Yanbo Zhang Yanxing Cai Lu Lu Shuai Xia Shibo Jiang
author_sort	Qiaoshuai Lan
title	25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses
title_short	25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses
title_full	25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses
title_fullStr	25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses
title_full_unstemmed	25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses
title_sort	25-hydroxycholesterol-conjugated ek1 peptide with potent and broad-spectrum inhibitory activity against sars-cov-2, its variants of concern, and other human coronaviruses
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cce3f0137fe845309189e2abf1f1776f
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25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses

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