COVIDYN

COVIDYN is led by Dr Himanshu Khandelia from the University of Southern Denmark, Denmark. The team will drive molecular dynamics (MD) simulations and Markov State Models to block viral entry into the human cells. It happens through an ectodomain of the trimeric S protein of the coronavirus. This domain of a membrane in SARS-CoV-2 is responsible for attachment to and entry into cells during infection. This project is unique in the sense that it concentrates on the conformational transitions in the S protein that make this binding possible and may point to new drug targets. According to the team, successful viral entry is contingent upon an optimal conformational equilibrium between the "up" (active) and "down" (inactive) conformations of the receptor binding domains (RBDs). They estimate that a lower population of "up" conformations is likely to block the viral entry. The group expects two impressive outcomes from their approach. The first one is to find conformational transitions of the RBDs from the "down" to "up" state for SARS-CoV and SARS-CoV-2. The second is to identify new druggable hotspots that drive these transitions. Therefore, these druggable hotspots can be targets for future antiviral development. Moreover, these studies will be obvious starting points for antibody and antiviral developments. At the end of the project the scientists want to verify their hypotheses as to why SARS-CoV-2 is more virulent than previous coronaviruses. All these complex studies and simulations require high computational power and PRACE awarded the team with 35 000 000 core hours on Piz Daint, hosted by CSCS, Switzerland.