SPIKE-CAP - Blocking SARS-CoV-2 Spike protein through Computer-Aided design of Peptide inhibitors

SPIKE-CAP - Blocking SARS-CoV-2 Spike protein through Computer-Aided design of Peptide inhibitors is a PRACE-awarded project led by Dr Alfonso Gautieri from the Polytechnic University of Milan, Italy. The SPIKE-CAP project aims to design antiviral peptides (short chains of amino acids, linked by peptide bonds) with ultra-high affinity for the coronavirus spike protein (S) by using high-throughput computational deep scanning mutagenesis. The most promising candidate will be tested by a partner lab at Massachusetts Institute of Technology (MIT) with bio-layer interferometry (BLI) and X-ray crystallography. Using a computational scanning mutagenesis method, developed at the Polytechnic University of Milan and based on Simulated Annealing Molecular Dynamics, the team will computationally screen peptide mutations and rank them by binding affinity to S protein, while a machine learning algorithm, developed by MIT, will ensure the correct helical folding. The project has the potential to identify peptides with ultra-high affinity to the spike of the virus, which would outcompete binding with human ACE2, thereby preventing viral infection. The team expects that this project could be helpful for future design of peptidie therapeutics. To support this innovative approach, PRACE awarded the project with 44 000 000 core hours on Marconi100, hosted by CINECA, Italy.