WP4 From target to hit


This work package, led by Dr. Bruno Canard (AMU), will develop novel hit series based on the public and proprietary knowledge available to the PANVIPREP consortium on viral targets essential for virus replication. These efforts will create promising starting points for broad(er)-spectrum antiviral drug discovery and development. The hit series discovered or expanded in WP4 are transferred to WP3 to be used as tool compounds for antiviral target validation. If exceptionally promising hit series are discovered, they may be transferred to WP2 for further hit-to-early-lead development, thus closing the loop of antiviral drug discovery and development, from target to new hit series.

WP4 tasks are organized into nine Mini-Projects (MPs), each organized around specific hit(s)/enzyme and/or virus types. The aim is to promote multidisciplinary collaboration and expedite the hit-iteration process, mainly by using proven hit families with an early lead as expected outcome. Some hits with great inhibition/binding properties but poor infected cell activity will be transferred to WP3, to be evaluated and included in the PROTAC approach.

WP4 will be capped and coordinated using an original management format called the SWIFT-HD (Specialized Workgroup for Integrating, Formatting, and Transfer of Hit Data), which will manage acquired data in preparation for AI/Machine Learning to expedite the drug development process.

List of PANVIPREP WP4 Mini-Projects:

  • MP1: Inhibitors of the corona/flavi/alphavirus RNA-MTase
  • MP2: Inhibitors of the coronavirus nsp7/8/12 RNA synthesis/editing engine
  • MP3: Inhibitors of the coronavirus nsp10/14 exonuclease (ExoN)
  • MP4: Inhibitors of the respiratory syncytial virus L-protein RdRp
  • MP5: Across-family broad-spectrum inhibitors of entero- and coronavirus proteases
  • MP6: Inhibitors of the enterovirus replication complex
  • MP7: Broad-spectrum Inhibitors of the flavivirus NS5 protein
  • MP8: Antivirals targeting positive-stranded RNA viral membrane-associated replication complexes
  • MP9: Inhibitors that target conserved and important viral RNA structures

 

Immunofluorescence microscopy of SARS-coronavirus-infected cells labeled for viral RNA (green), membrane (M) protein (red), and nuclear DNA (blue).