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本文引用的文献

1
High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses.高通量筛选和鉴定冠状病毒广谱强效抑制剂。
J Virol. 2019 May 29;93(12). doi: 10.1128/JVI.00023-19. Print 2019 Jun 15.
2
Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry.依米丁通过两种分子机制抑制寨卡病毒和埃博拉病毒感染:抑制病毒复制和减少病毒进入。
Cell Discov. 2018 Jun 5;4:31. doi: 10.1038/s41421-018-0034-1. eCollection 2018.
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Dasatinib dose management for the treatment of chronic myeloid leukemia.达沙替尼治疗慢性髓性白血病的剂量管理。
Cancer. 2018 Apr 15;124(8):1660-1672. doi: 10.1002/cncr.31232. Epub 2018 Jan 25.
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Antiviral activity of cationic amphiphilic drugs.阳离子两亲性药物的抗病毒活性。
Expert Rev Anti Infect Ther. 2017 May;15(5):483-492. doi: 10.1080/14787210.2017.1305888. Epub 2017 Mar 20.
5
Efficacy and Mechanism of Action of Low Dose Emetine against Human Cytomegalovirus.低剂量吐根碱抗人巨细胞病毒的疗效及作用机制
PLoS Pathog. 2016 Jun 23;12(6):e1005717. doi: 10.1371/journal.ppat.1005717. eCollection 2016 Jun.
6
Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia.沙特阿拉伯王国一家冠状病毒转诊中心中东呼吸综合征冠状病毒(MERS-CoV)感染患者的治疗结果。
BMC Infect Dis. 2016 Apr 21;16:174. doi: 10.1186/s12879-016-1492-4.
7
Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.系统性红斑狼疮患者的羟氯喹血药浓度:阐明给药争议并提高依从性
J Rheumatol. 2015 Nov;42(11):2092-7. doi: 10.3899/jrheum.150379. Epub 2015 Oct 1.
8
Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset.洛匹那韦/利托那韦或干扰素-β1b治疗可改善普通狨猴中东呼吸综合征冠状病毒感染非人灵长类动物模型的预后。
J Infect Dis. 2015 Dec 15;212(12):1904-13. doi: 10.1093/infdis/jiv392. Epub 2015 Jul 21.
9
Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity.天然植物生物碱(吐根碱)通过干扰逆转录酶活性抑制HIV-1复制。
Molecules. 2015 Jun 22;20(6):11474-89. doi: 10.3390/molecules200611474.
10
Testing of Middle East respiratory syndrome coronavirus replication inhibitors for the ability to block viral entry.对中东呼吸综合征冠状病毒复制抑制剂进行阻断病毒进入能力的测试。
Antimicrob Agents Chemother. 2015 Jan;59(1):742-4. doi: 10.1128/AAC.03977-14. Epub 2014 Oct 20.

吐根碱、吐根、吐根生物碱及其类似物作为冠状病毒的潜在抗病毒药物

Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses.

作者信息

Bleasel Martin D, Peterson Gregory M

机构信息

School of Pharmacy and Pharmacology, University of Tasmania, Hobart Tasmania 7001, Australia.

出版信息

Pharmaceuticals (Basel). 2020 Mar 21;13(3):51. doi: 10.3390/ph13030051.

DOI:10.3390/ph13030051
PMID:32245264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7151655/
Abstract

The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative ECs of emetine towards the coronaviruses compared with , emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.

摘要

新型冠状病毒肺炎(COVID-19)目前正在全球传播,可用的治疗选择有限。本文阐述了使用曾用于治疗阿米巴病的旧药(吐根碱、其他吐根生物碱或类似物)来治疗COVID-19的理论依据。在针对中东呼吸综合征(MERS)和严重急性呼吸综合征(SARS)冠状病毒筛选的290多种药物中,吐根碱的半数最大有效浓度(EC)报告值是最低的。虽然吐根碱在血液中可达到相应浓度,但研究表明,其在肺部的浓度可能几乎高出300倍。此外,基于吐根碱对冠状病毒的相对EC值与……相比,吐根碱作为一种抗冠状病毒药物可能比对阿米巴病更有效。本文还讨论了吐根碱及相关化合物已知的副作用、如何处理这些副作用以及对COVID-19进行潜在治疗的最佳给药方法。鉴于COVID-19冠状病毒构成的严重且紧迫的威胁、我们使用吐根碱的悠久历史以及吐根碱在肺部达到治疗浓度的可能性,吐根、吐根碱及其他类似物应被视为潜在的治疗选择,特别是如果体外研究证实病毒敏感性。