Halogenated Rocaglate Derivatives: Pan-antiviral Agents against Hepatitis E Virus and Emerging Viruses
Catherine Victoria, Göran Schulz, Mara Klöhn, Saskia Weber, Cora M. Holicki, Yannick Brüggemann, Miriam Becker, Gisa Gerold, Martin Eiden, Martin H. Groschup, Eike Steinmann, Andreas Kirschning
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.