A drug discovery project against the main protease of COVID-19

A drug discovery project against the main protease of COVID-19 is led by Prof. Maria João Ramos from the University of Porto, Portugal. With this project, she and her team propose to develop drugs for one particular target and this is the main protease of the virus, caused COVID-19. If this main protease enzyme is blocked and it cannot function properly, the virus will not replicate. The process can be facilitated by using available good resolution x-ray structures of this protease in 2020 in the Protein Data Bank. Subsequently, the scientists will put forward two studies, carried out in parallel to make a list of compounds with anti-virus activity. They will perform Virtual Screening (VS) with protein-ligand docking methodologies to estimate binding sites. They will use protocols and scoring functions and will test not only commercial compound libraries containing millions of compounds, but also their in-house developed compound library, again with millions of compounds. The goal is to identify new chemical entities that can potentially bind to the selected protein target. Also, the group will identify drugs that must still be active upon the enzyme modifications. This will be done with molecular modelling and molecular dynamics, using Free Energy Perturbation techniques. PRACE awarded the project with 370 000 node hours on Piz Daint hosted by CSCS, Switzerland.