2. Academic Validation
  3. Halogenated Rocaglate Derivatives: Pan-antiviral Agents against Hepatitis E Virus and Emerging Viruses

Halogenated Rocaglate Derivatives: Pan-antiviral Agents against Hepatitis E Virus and Emerging Viruses

  • J Med Chem. 2024 Jan 11;67(1):289-321. doi: 10.1021/acs.jmedchem.3c01357.
Catherine Victoria 1,  Göran Schulz 1,  Mara Klöhn 2,  Saskia Weber 3,  Cora M Holicki 3,  Yannick Brüggemann 2,  Miriam Becker 4,  Gisa Gerold 4 5 6,  Martin Eiden 3,  Martin H Groschup 3,  Eike Steinmann 2,  Andreas Kirschning 1
Affiliations

Affiliations

  • 1 Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover, Germany.
  • 2 Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany.
  • 3 Federal Research Institute in Animal Health (FLI), Südufer 10, 17493 Greifswald, Insel Riems, Germany.
  • 4 Institute for Biochemistry and Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Bünteweg 2, 30559 Hannover, Germany.
  • 5 Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 901 87 Umeå, Sweden.
  • 6 Department of Clinical Microbiology, Virology, Umeå University, 901 87 Umeå, Sweden.
PMID: 38127656 DOI: 10.1021/acs.jmedchem.3c01357
Abstract

The synthesis of a library of halogenated rocaglate derivatives belonging to the flavagline class of Natural Products, of which silvestrol is the most prominent example, is reported. Their Antiviral activity and cytotoxicity profile against a wide range of pathogenic viruses, including hepatitis E, Chikungunya, Rift Valley Fever virus and SARS-CoV-2, were determined. The incorporation of halogen substituents at positions 4', 6 and 8 was shown to have a significant effect on the Antiviral activity of rocaglates, some of which even showed enhanced activity compared to CR-31-B and silvestrol.

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