Revealing the molecular mechanisms of proteolysis of SARS-CoV-2 M <sup>pro</sup> by QM/MM computational methods
Katarzyna Świderek, Vicent Moliner
Abstract
is one of the enzymes essential for the replication process of the virus responsible for the COVID-19 pandemic. This work is focused on exploring its proteolysis reaction by means of QM/MM methods. The resulting free energy landscape of the process provides valuable information on the species appearing along the reaction path and suggests that the mechanism of action of this enzyme, taking place in four steps, slightly differs from that of other cysteine proteases. Our predictions, which are in agreement with some recently published experimental data, can be used to guide the design of COVID-19 antiviral compounds with clinical potential.
Topics & Concepts
ProteolysisEnzymeChemistryQM/MMSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)Mechanism (biology)Molecular dynamicsBiochemistryComputational chemistryPhysicsDiseaseMedicineInfectious disease (medical specialty)Quantum mechanicsPathologyProtein Structure and DynamicsEnzyme Structure and FunctionComputational Drug Discovery Methods