B5: Development of Dithiocarbamates as Anthelminthics and Inhibitors of RNA-helicase eIF4A as potential antiviral Agents

Project description:

Helminthic infections represent a major problem in large parts of the world. In comparison to the burden the arsenal of anthelminthic drugs is rather limited. Using successive cycles of design, synthesis and testing the novel class of dithiocarbamates shall be optimized regarding activity towards different helminths, host toxicity and drug-likeness. Derivatives are synthesized, tested against different helminths and human cell lines. For promising derivatives ADME-parameters are determined and selected compounds could be tested in vivo.

Different viruses pathogenic to humans, as for instance the Ebola- or the SARS-CoV-2 virus, are using host factors for intracellular replication. These host factors therefor represent a target for anti-viral drug design. One of these host factors is the RNA-helicase eIF4A. Based on the crystal structure of the eIF4A-RNA complex appropriate ligands are designed, evaluated by docking and in case of proper fit synthesized. Compounds are tested in regard to their effect on translation efficiency. Active derivatives are subsequently evaluated regarding their effect on virus replication in cell cultures.

Scientific goal:

Both projects should yield compounds which possess the quality of a lead structure or possibly a development candidate

DRUID Collaboration partners:

A2, A3, A4, A7, B2, B7P, C6 NWG, D4, E1, E4, E6

References B5: –