Amaryllidaceae Alkaloids Screen Unveils Potent Anticoronaviral Compounds and Associated Structural Determinants

IF 4.9 Q1 CHEMISTRY, MEDICINAL
Natacha Merindol, Luan Letieri Belem Martins, Ghada Elfayres, Alexandre Custeau, Lionel Berthoux, Antonio Evidente and Isabel Desgagné-Penix*, 
{"title":"Amaryllidaceae Alkaloids Screen Unveils Potent Anticoronaviral Compounds and Associated Structural Determinants","authors":"Natacha Merindol,&nbsp;Luan Letieri Belem Martins,&nbsp;Ghada Elfayres,&nbsp;Alexandre Custeau,&nbsp;Lionel Berthoux,&nbsp;Antonio Evidente and Isabel Desgagné-Penix*,&nbsp;","doi":"10.1021/acsptsci.4c0042410.1021/acsptsci.4c00424","DOIUrl":null,"url":null,"abstract":"<p >Betacoronaviruses encompass a spectrum of respiratory diseases, from common cold caused by the human coronavirus (HCoV)-OC43 to life-threatening severe acute respiratory syndrome (SARS)-CoV-2. Addressing the constant need for novel antiviral compounds, we turned to the exploration of 40 plant-specialized metabolites produced by the medicinal plant family Amaryllidaceae, known to produce lycorine, a strong antiviral alkaloid. The present screen included 35 alkaloids with representatives of 8 ring-type structures. Pancracine, crinamine, hemanthamine, and hemanthidine exhibited potency comparable to lycorine in blocking HCoV–OC43 replication, while amarbellisine demonstrated superior efficacy (SI = 60, EC<sub>50</sub> = 0.2 μM). Their anticoronaviral activity was confirmed using a SARS-CoV-2 replicon system. Time-of-drug-addition experiments established that a postentry step consistent with ribonucleic acid (RNA) replication or translation was targeted. Most antiviral Amaryllidaceae alkaloids selectively induced the expression of transcripts associated with the integrated stress response. Structure–activity relationship analyses elucidated key functional groups contributing to antiviral properties in the crinine- and lycorine-type. This study reveals that Amaryllidaceae produce a diverse repertoire of promising antiviral compounds in addition to lycorine, offering insights for developing new antiviral agents.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"7 11","pages":"3527–3539 3527–3539"},"PeriodicalIF":4.9000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Pharmacology and Translational Science","FirstCategoryId":"1085","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsptsci.4c00424","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Betacoronaviruses encompass a spectrum of respiratory diseases, from common cold caused by the human coronavirus (HCoV)-OC43 to life-threatening severe acute respiratory syndrome (SARS)-CoV-2. Addressing the constant need for novel antiviral compounds, we turned to the exploration of 40 plant-specialized metabolites produced by the medicinal plant family Amaryllidaceae, known to produce lycorine, a strong antiviral alkaloid. The present screen included 35 alkaloids with representatives of 8 ring-type structures. Pancracine, crinamine, hemanthamine, and hemanthidine exhibited potency comparable to lycorine in blocking HCoV–OC43 replication, while amarbellisine demonstrated superior efficacy (SI = 60, EC50 = 0.2 μM). Their anticoronaviral activity was confirmed using a SARS-CoV-2 replicon system. Time-of-drug-addition experiments established that a postentry step consistent with ribonucleic acid (RNA) replication or translation was targeted. Most antiviral Amaryllidaceae alkaloids selectively induced the expression of transcripts associated with the integrated stress response. Structure–activity relationship analyses elucidated key functional groups contributing to antiviral properties in the crinine- and lycorine-type. This study reveals that Amaryllidaceae produce a diverse repertoire of promising antiviral compounds in addition to lycorine, offering insights for developing new antiviral agents.

Abstract Image

金盏花科生物碱筛选出强效抗oronaviral 化合物及相关结构决定因素
β冠状病毒包括一系列呼吸道疾病,从由人类冠状病毒(HCoV)-OC43 引起的普通感冒到危及生命的严重急性呼吸系统综合征(SARS)-CoV-2。为了满足对新型抗病毒化合物的持续需求,我们转而探索药用植物天南星科(Amaryllidaceae)产生的 40 种植物专有代谢物。本次筛选包括 35 种生物碱,代表 8 种环状结构。Pancracine、crinamine、hemanthamine 和 hemanthidine 在阻断 HCoV-OC43 复制方面的效力与 lycorine 相当,而 amarbellisine 则表现出更高的效力(SI = 60,EC50 = 0.2 μM)。使用 SARS-CoV-2 复制子系统证实了它们的抗冠状病毒活性。加药时间实验证明,它们针对的是与核糖核酸(RNA)复制或翻译一致的后进入步骤。大多数抗病毒的金丝桃科生物碱都能选择性地诱导与综合应激反应相关的转录本的表达。通过结构-活性关系分析,阐明了在松脂型和番茄红素型抗病毒特性中起作用的关键功能基团。这项研究揭示了除番茄红素外,金盏花科植物还产生了多种有潜力的抗病毒化合物,为开发新的抗病毒药物提供了启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
ACS Pharmacology and Translational Science
ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)
CiteScore
10.00
自引率
3.30%
发文量
133
期刊介绍: ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信