Targeting the Lysosome-Endosome system to avoid virus entry/exit in cells

The project entitled Targeting the Lysosome-Endosome system to avoid virus entry/exit in cells is led by Prof. Matteo Ceccarelli from the University of Cagliari, Italy. This is an unconventional project with a chance for breakthroughs not only in the battle against the COVID-19, but also for other diseases like cancer and Parkinson. In the project, the team proposes another strategy, less direct, but with a larger potential. It is based on the investigation of an unexplored key target: the lysosomal-endosomal TPC2 ion channels of the two-pore channel family. This system is involved in the trafficking of cells. The lysosome is a small organelle of cells and its interior is an acid to allow molecule degradation by internal enzymes. It has primary importance for many cell processes and it is involved in different diseases, such as cancer and Parkinson, as well as in viral infections. For example, in 2015 it was proven how its inhibition could stop Ebola, and after that, MERS-CoV as well. Therefore, TPC2 is a target with a high potential for the development of antiviral compounds. The team has been working on TPC channels for two years and investigated them by using molecular dynamics and metadynamics simulations. The scientists already started the docking (method for predicting binding of two molecules in stable complex) of a flavonoid of TPC2 as a possible target against cancer. In their current project they have two main objectives: 1) to understand the mechanism of functioning of TPC2, and 2) its potentiality as a target for antiviral compounds of the flavonoid family. The team expects that they will verify up to five docking sites. It could be a chance not only for discovering antiviral compounds but also for breakthroughs against cancer and Parkinson. Because the project requires substantial computational power, PRACE awarded the group with 7 920 000 core hours on Marconi100, hosted by CINECA, Italy.