Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis.

Rationale: The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown.

Objectives: To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza.

3,5-Diphenylpent-2-enoic acids as allosteric activators of the protein kinase PDK1: structure-activity relationships and thermodynamic characterization of binding as paradigms for PIF-binding pocket-targeting compounds.

The modulation of protein kinase activities by low molecular weight compounds is a major goal of current pharmaceutical developments. In this line, important efforts are directed to the development of drugs targeting the conserved ATP binding site. However, there is very little experience on targeting allosteric, regulatory sites, different from the ATP binding site, in protein kinases.

Allosteric activation of the protein kinase PDK1 with low molecular weight compounds.

Organisms rely heavily on protein phosphorylation to transduce intracellular signals. The phosphorylation of a protein often induces conformational changes, which are responsible for triggering downstream cellular events. Protein kinases are themselves frequently regulated by phosphorylation.