Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations
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.PMID:38228190 | PMC:PMC10831786 | DOI:10.1016/j.virusres.2024.199322
Source: Virus Research - Category: Virology Authors: Viktoriya S Sidorenko Ira Cohen Kunchok Dorjee Concei ção 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 Ch Source Type: research
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