Identification of structurally re-engineered rocaglates as inhibitors against hepatitis E virus replication.

Antiviral Agents / pharmacology Hepatitis E / drug therapy Hepatitis E virus Humans Interferon-alpha / pharmacology Ribavirin / pharmacology Virus Replication
Amidino-rocaglates Antiviral treatment Antivirals Hepatitis E virus elF4A inhibitors

Journal

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

Informations de publication

Date de publication:
08 2022
Historique:
received: 12 03 2022
revised: 16 05 2022
accepted: 06 06 2022
pubmed: 22 6 2022
medline: 14 7 2022
entrez: 21 6 2022
Statut: ppublish

Résumé

Hepatitis E virus (HEV) infections are a leading cause of acute viral hepatitis in humans and pose a considerable threat to public health. Current standard of care treatment is limited to the off-label use of nucleoside-analog ribavirin (RBV) and PEGylated interferon-α, both of which are associated with significant side effects and provide limited efficacy. In the past few years, a promising natural product compound class of eukaryotic initiation factor 4A (eIF4A) inhibitors (translation initiation inhibitors), called rocaglates, were identified as antiviral agents against RNA virus infections. In the present study, we evaluated a total of 205 synthetic rocaglate derivatives from the BU-CMD compound library for their antiviral properties against HEV. At least eleven compounds showed inhibitory activities against the HEV genotype 3 (HEV-3) subgenomic replicon below 30 nM (EC

Identifiants

DOI: 10.1016/j.antiviral.2022.105359 PMID: 35728703 PMC: PMC9731315
pubmed: 35728703
pii: S0166-3542(22)00128-0
doi: 10.1016/j.antiviral.2022.105359
pmc: PMC9731315
mid: NIHMS1852111
pii:
doi:

Substances chimiques

Antiviral Agents 0
Interferon-alpha 0
Ribavirin 49717AWG6K

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

105359

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM118173
Pays : United States
Organisme : NCATS NIH HHS
ID : U01 TR002625
Pays : United States

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

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Auteurs

Dimas F Praditya (DF)

Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany; Research Center for Vaccine and Drugs, The National Research and Innovation Agency, Cibinong, Indonesia. Electronic address: dima009@brin.go.id.

Mara Klöhn (M)

Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany. Electronic address: Mara.Kloehn@rub.de.

Yannick Brüggemann (Y)

Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany. Electronic address: Yannick.Brueggemann@rub.de.

Lauren E Brown (LE)

Department of Chemistry, Boston University, Boston, MA, 02215, USA; Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA, USA. Electronic address: brownle@bu.edu.

John A Porco (JA)

Department of Chemistry, Boston University, Boston, MA, 02215, USA; Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA, USA. Electronic address: porco@bu.edu.

Wenhan Zhang (W)

Department of Chemistry, Boston University, Boston, MA, 02215, USA; Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA, USA. Electronic address: wenhanzh@bu.edu.

Volker Kinast (V)

Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany; Department of Medical Microbiology and Virology, Carl von Ossietzky University Oldenburg, Oldenburg, Germany. Electronic address: Volker.Kinast@rub.de.

Andreas Kirschning (A)

Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167, Hannover, Germany. Electronic address: andreas.kirschning@oci.uni-hannover.de.

Florian W R Vondran (FWR)

ReMediES, Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany. Electronic address: Vondran.Florian@mh-hannover.de.

Daniel Todt (D)

Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany; European Virus Bioinformatics Center (EVBC), 07743, Jena, Germany. Electronic address: Daniel.Todt@rub.de.

Eike Steinmann (E)

Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany; German Centre for Infection Research (DZIF), External Partner Site, Bochum, Germany. Electronic address: Eike.Steinmann@rub.de.

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Classifications MeSH

Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Identification of structurally re-engineered...
Recherchemedicale.com › Maladies de l'appareil digestif › Maladies du foie › Hépatite › Hépatites virales humaines › Hépatite E › Identification of structurally re-engineered...
Recherchemedicale.com › Virus › Virus à ARN › Virus à ARN à brin positif › Hepevirus › Virus de l'hépatite E › Identification of structurally re-engineered...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification of structurally re-engineered...
Recherchemedicale.com › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › Interféron alpha › Identification of structurally re-engineered...
Recherchemedicale.com › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Ribonucléosides › Ribavirine › Identification of structurally re-engineered...
Recherchemedicale.com › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Identification of structurally re-engineered...