Silver N-heterocyclic carbene complexes are potent uncompetitive inhibitors of the papain-like protease with antiviral activity against SARS-CoV-2
María Gil‐Moles, Cillian O’Beirne, Igor V. Esarev, Petra Lippmann, Matthias Tacke, Jindřich Činátl, Denisa Bojková, Ingo Ott
Abstract
as relevant factor of their activity. In addition, enzyme kinetic experiments revealed that the complex is an uncompetitive inhibitor and with this rare type of inhibition it offers great pharmacological advantages in terms selectivity. The silver NHC complexes with iodide ligands showed very low or absent host cell toxicity and triggered strong effects on viral replication in cells infected with SARS-CoV-2, making them promising future antiviral drug candidates.
Topics & Concepts
ProteasePapainUncompetitive inhibitorEnzymeChemistryProtease inhibitor (pharmacology)BiochemistrySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)BiologyVirologyCoronavirus disease 2019 (COVID-19)Non-competitive inhibitionVirusMedicineDiseaseInfectious disease (medical specialty)Antiretroviral therapyViral loadPathologyN-Heterocyclic Carbenes in Organic and Inorganic ChemistryQuinazolinone synthesis and applicationsPneumocystis jirovecii pneumonia detection and treatment