A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics
Jonas Goßen, Simone Albani, Anton Hanke, Benjamin P. Joseph, Cathrine Bergh, Maria Kuzikov, Elisa Costanzi, Candida Manelfi, Paola Storici, Philip Gribbon, Andrea R. Beccari, Carmine Talarico, Francesca Spyrakis, Erik Lindahl, Andrea Zaliani, Paolo Carloni, Rebecca C. Wade, Francesco Musiani, Daria B. Kokh, Giulia Rossetti
Abstract
assays performed here and by a newly solved X-ray crystal structure. These results provide a strong basis for effective rational drug design campaigns against SARS-CoV-2 Mpro and a new computational approach to screen protein targets with malleable binding sites.
Topics & Concepts
PharmacophoreDruggabilityComputational biologyVirtual screeningChemistryLigand (biochemistry)Binding siteBinding affinitiesProteaseDrug discoveryStereochemistryBiologyEnzymeBiochemistryReceptorGeneComputational Drug Discovery MethodsSARS-CoV-2 and COVID-19 ResearchProtein Structure and Dynamics