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

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.