Targeting conformational changes implicated in early events of viral entry

Targeting conformational changes implicated in early events of viral entry is a project devising another trap to catch the virus. The project is that of Prof. Francisco Javier Luque from the University of Barcelona in Spain. It has two ambitious goals. First, to disrupt viral entry by finding small molecules able to interfere with the conformational changes in the spike protein, prior to binding to the host cell. Second to characterise the structural and energetic changes, implicated in transition in both free and ligand-bound spike proteins. The team of Prof. Luque has a precise model of this collaboration between a spike and human cell receptor and found a specific inactive state. The scientists would like to find a small compound that might stabilise it. They will attempt this through binding to a pocket located at the hinge region, which defines a putative druggable cavity. This was estimated from two independent druggability predictors. These stabilisers are hiding the determinants of ACE2 binding and the disclosure of a moderate stabiliser could be a promising finding. PRACE awarded the project 15 300 000 core hours on Hawk, hosted by GCS at HLRS, Germany.