Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses.

A549 Cells Animals Anisomycin / pharmacology Antiviral Agents / pharmacology Chlorocebus aethiops Dengue / drug therapy Dengue Virus / drug effects Female Humans Male Mice Vero Cells Virus Replication / drug effects Zika Virus / drug effects Zika Virus Infection / drug therapy
Anisomycin Antiviral Dengue Flavivirus Zika p38

Journal

Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699

Informations de publication

Date de publication:
04 2020
Historique:
received: 13 08 2019
revised: 21 01 2020
accepted: 15 02 2020
pubmed: 23 2 2020
medline: 12 1 2021
entrez: 22 2 2020
Statut: ppublish

Résumé

Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replication of reference strains and clinical isolates of all DENV serotypes and Asian and African strains of ZIKV in Vero cells. Anisomycin also prevented DENV and ZIKV multiplication in human cell lines. While initial steps of DENV and ZIKV replicative cycle were unaffected, a high inhibition of viral protein expression was demonstrated after treatment with anisomycin. DENV RNA synthesis was strongly reduced in anisomycin treated cultures, but the compound did not exert a direct inhibitory effect on 2' O-methyltransferase or RNA polymerase activities of DENV NS5 protein. Furthermore, anisomycin-mediated activation of p38 signaling was not related to the antiviral action of the compound. The evaluation of anisomycin efficacy in a mouse model of ZIKV morbidity and mortality revealed that animals treated with a low dose of anisomycin exhibited a significant reduction in viremia levels and died significantly later than the control group. This protective effect was lost at higher doses, though. In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model.

Identifiants

DOI: 10.1016/j.antiviral.2020.104749 PMID: 32081740 PMC: PMC7279513
pubmed: 32081740
pii: S0166-3542(19)30461-9
doi: 10.1016/j.antiviral.2020.104749
pmc: PMC7279513
mid: NIHMS1566819
pii:
doi:

Substances chimiques

Antiviral Agents 0
Anisomycin 6C74YM2NGI

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

104749

Subventions

Organisme : NIAID NIH HHS
ID : HHSN272201700041I
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

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Auteurs

V M Quintana (VM)

Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires/ IQUIBICEN (CONICET), Ciudad Universitaria, Pabellón 2, Piso 4, Buenos Aires, 1428, Argentina. Electronic address: vmquintana@qb.fcen.uba.ar.

B Selisko (B)

Centre National de la Recherche Scientifique (CNRS) and Aix-Marseille Université (AMU), Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB) UMR 7257, 163 Avenue de Luminy, 13288, Marseille Cedex 9, France. Electronic address: barbara.selisko@afmb.univ-mrs.fr.

J E Brunetti (JE)

Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires/ IQUIBICEN (CONICET), Ciudad Universitaria, Pabellón 2, Piso 4, Buenos Aires, 1428, Argentina. Electronic address: jebrunetti@qb.fcen.uba.ar.

C Eydoux (C)

Centre National de la Recherche Scientifique (CNRS) and Aix-Marseille Université (AMU), Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB) UMR 7257, 163 Avenue de Luminy, 13288, Marseille Cedex 9, France. Electronic address: cecilia.eydoux@afmb.univ-mrs.fr.

J C Guillemot (JC)

Centre National de la Recherche Scientifique (CNRS) and Aix-Marseille Université (AMU), Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB) UMR 7257, 163 Avenue de Luminy, 13288, Marseille Cedex 9, France. Electronic address: jean-claude.guillemot@afmb.univ-mrs.fr.

B Canard (B)

Centre National de la Recherche Scientifique (CNRS) and Aix-Marseille Université (AMU), Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB) UMR 7257, 163 Avenue de Luminy, 13288, Marseille Cedex 9, France. Electronic address: Bruno.Canard@afmb.univ-mrs.fr.

E B Damonte (EB)

Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires/ IQUIBICEN (CONICET), Ciudad Universitaria, Pabellón 2, Piso 4, Buenos Aires, 1428, Argentina. Electronic address: edamonte@qb.fcen.uba.ar.

J G Julander (JG)

Institute for Antiviral Research, Utah State University, Logan, UT, USA. Electronic address: justin.julander@usu.edu.

V Castilla (V)

Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires/ IQUIBICEN (CONICET), Ciudad Universitaria, Pabellón 2, Piso 4, Buenos Aires, 1428, Argentina. Electronic address: viviana@qb.fcen.uba.ar.

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules A549 › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Eucaryotes › Animaux › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrrolidines › Anisomycine › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Cercopithecus › Cercopithecus aethiops › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ARN › Fièvres hémorragiques virales › Dengue › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Flaviviridae › Flavivirus › Virus de la dengue › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules Vero › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Flaviviridae › Flavivirus › Virus Zika › Antiviral activity of the natural alkaloid...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ARN › Infections à Flaviviridae › Infections à flavivirus › Infection par le virus Zika › Antiviral activity of the natural alkaloid...