Virus Research (Mar 2024)
Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations
- 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
Affiliations
- Viktoriya S. Sidorenko
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
- Ira Cohen
- Department of Physiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Kunchok Dorjee
- Division of Infectious Diseases, John Hopkins School of Medicine, Baltimore, Maryland 21205, USA
- Conceição A. Minetti
- Department of Chemistry and Chemical Biology, Rutgers – The State University of New Jersey, Piscataway, New Jersey 08854, USA
- David P. Remeta
- Department of Chemistry and Chemical Biology, Rutgers – The State University of New Jersey, Piscataway, New Jersey 08854, USA
- Junyuan Gao
- Department of Physiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Irina Potapova
- Department of Physiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Hong Zhan Wang
- Department of Physiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Janet Hearing
- Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Wan-Yi Yen
- Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Hwan Keun Kim
- Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Keiji Hashimoto
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
- Masaaki Moriya
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
- Kathleen G. Dickman
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of Medicine, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Xingyu Yin
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
- Miguel Garcia-Diaz
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
- Rajesh Chennamshetti
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
- Radha Bonala
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
- Francis Johnson
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of Chemistry, Stony Brook University, Stony Brook, New York 11794, USA
- Amanda L. Waldeck
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of Pharmacy, Stony Brook University Hospital, Stony Brook, New York 11794, USA
- Ramesh Gupta
- ChemMaster International Inc., Happauge, New York 11788, USA
- Chaoping Li
- Chemistry Service Unit of Shanghai Haoyuan Chemexpress Co., Ltd., Shanghai, PR China 201203
- Kenneth J. Breslauer
- Department of Chemistry and Chemical Biology, Rutgers – The State University of New Jersey, Piscataway, New Jersey 08854, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA
- Arthur P. Grollman
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of Medicine, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- Thomas A. Rosenquist
- Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Corresponding author at: Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
- Journal volume & issue
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Vol. 341
p. 199322
Abstract
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.
