Roadmap for development of therapeutics for helminths

What are we trying to achieve and why? What is the problem we are trying to solve?

• Genomic-assisted drug discovery and/or other screening-based technologies should shortly come up with some novel molecules active against multi-resistant helminth parasites.
• Is it possible to design a new anthelmintic molecule based on the knowledge of a biomolecular drug target?

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

• Further knowledge on basic pharmacodynamic aspects related to anthelmintic activity is needed. The response to the following questions are the main scientific challenges to design novel anthelmintic molecules:
• Are there new/alternative potential drug binding sites in traditional (well known) molecular targets?
• Can we find potential drug binding sites in other new biomolecular binding targets?
• Which are the ´pharmacophores´ (molecular features that are necessary for molecular recognition of a ligand by a biological macromolecule)of each anthelmintic moleculeat their specific receptors?

What approaches could/should be taken to address the research question?

• Determine the three-dimensional structure of biomolecular helminth parasite targets.
• Determine the potential binding sites of those biomolecular targets.
• Determine the pharmacophoric points on each biomolecular helminth parasite target.
• Search for new potential anthelmintic drugs using computer-based methods of drug design.

What else needs to be done before we can solve this need?

A clear identification of the true biomolecular target/s (the target/s responsible for drug effect) for each anthelmintic (traditional and novel compounds).

Existing knowledge including successes and failures

Current on-going work is focussed on the understanding of the pharmacodynamic basis of anthelmintic action for most of the available anthelmintic molecules.