دورية أكاديمية
Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations
| العنوان: | Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations |
|---|---|
| المؤلفون: | Viktoriya S. Sidorenko, Ira Cohen, Kunchok Dorjee, Conceição A. Minetti, David P. Remeta, Junyuan Gao, Irina Potapova, Hong Zhan Wang, Janet Hearing, Wan-Yi Yen, Hwan Keun Kim, Keiji Hashimoto, Masaaki Moriya, Kathleen G. Dickman, Xingyu Yin, Miguel Garcia-Diaz, Rajesh Chennamshetti, Radha Bonala, Francis Johnson, Amanda L. Waldeck, Ramesh Gupta, Chaoping Li, Kenneth J. Breslauer, Arthur P. Grollman, Thomas A. Rosenquist |
| المصدر: | Virus Research, Vol 341, Iss , Pp 199322- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Microbiology LCC:Infectious and parasitic diseases |
| مصطلحات موضوعية: | Emetine, Dehydroemetine, SARS-CoV-2, Coronoviruses, Antiviral, Microbiology, QR1-502, Infectious and parasitic diseases, RC109-216 |
| الوصف: | The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC50 ∼ 50–100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC50 ∼ 40–60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1872-7492 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0168170224000157; https://doaj.org/toc/1872-7492 |
| DOI: | 10.1016/j.virusres.2024.199322 |
| URL الوصول: | https://doaj.org/article/504d0a1ccfe34d75ad6fc4310a4d74a1 |
| رقم الأكسشن: | edsdoj.504d0a1ccfe34d75ad6fc4310a4d74a1 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18727492 |
|---|---|
| DOI: | 10.1016/j.virusres.2024.199322 |