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Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations.
Sidorenko, Viktoriya S; Cohen, Ira; Dorjee, Kunchok; Minetti, Conceição A; Remeta, David P; Gao, Junyuan; Potapova, Irina; Wang, Hong Zhan; Hearing, Janet; Yen, Wan-Yi; Kim, Hwan Keun; Hashimoto, Keiji; Moriya, Masaaki; Dickman, Kathleen G; Yin, Xingyu; Garcia-Diaz, Miguel; Chennamshetti, Rajesh; Bonala, Radha; Johnson, Francis; Waldeck, Amanda L; Gupta, Ramesh; Li, Chaoping; Breslauer, Kenneth J; Grollman, Arthur P; Rosenquist, Thomas A.
Afiliación
  • Sidorenko VS; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
  • Cohen I; Department of Physiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
  • Dorjee K; Division of Infectious Diseases, John Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
  • Minetti CA; Department of Chemistry and Chemical Biology, Rutgers - The State University of New Jersey, Piscataway, New Jersey 08854, USA.
  • Remeta DP; Department of Chemistry and Chemical Biology, Rutgers - The State University of New Jersey, Piscataway, New Jersey 08854, USA.
  • Gao J; Department of Physiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
  • Potapova I; Department of Physiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
  • Wang HZ; Department of Physiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
  • Hearing J; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
  • Yen WY; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
  • Kim HK; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
  • Hashimoto K; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
  • Moriya M; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
  • Dickman KG; 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.
  • Yin X; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
  • Garcia-Diaz M; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
  • Chennamshetti R; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
  • Bonala R; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
  • Johnson F; 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.
  • Waldeck AL; 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.
  • Gupta R; ChemMaster International Inc., Happauge, New York 11788, USA.
  • Li C; Chemistry Service Unit of Shanghai Haoyuan Chemexpress Co., Ltd., Shanghai, PR China 201203.
  • Breslauer KJ; 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.
  • Grollman AP; 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.
  • Rosenquist TA; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: thomas.rosenquist@stonybrook.edu.
Virus Res ; 341: 199322, 2024 03.
Article en En | MEDLINE | ID: mdl-38228190
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Emetina / Alcaloides Límite: Humans Idioma: En Revista: Virus Res Asunto de la revista: VIROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Emetina / Alcaloides Límite: Humans Idioma: En Revista: Virus Res Asunto de la revista: VIROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos