Mechanism of inhibition of SARS-CoV-2 M <sup>pro</sup> by N3 peptidyl Michael acceptor explained by QM/MM simulations and design of new derivatives with tunable chemical reactivity
Kemel Arafet, Natalia Serrano-Aparicio, Alessio Lodola, Adrian J. Mulholland, Florenci V. González, Katarzyna Świderek, Vicent Moliner
Abstract
QM/MM simulations identify the mechanism of reaction of N3, a covalent peptidyl inhibitor of SARS-CoV-2 main protease. Modelling of two novel proposed compounds, B1 and B2, suggests that reversibility of covalent inhibition could be tailored.
Topics & Concepts
Reactivity (psychology)AcceptorMichael reactionChemistryMechanism (biology)Combinatorial chemistryStereochemistryComputational chemistryOrganic chemistryCatalysisPhysicsMedicinePathologyQuantum mechanicsAlternative medicineCondensed matter physicsComputational Drug Discovery MethodsChemical Synthesis and AnalysisPeptidase Inhibition and Analysis