Natural Compounds Inhibit SARS-CoV-2 nsp13 Unwinding and ATPase Enzyme Activities
Angela Corona, Krzysztof Wycisk, Carmine Talarico, Candida Manelfi, Jessica Milia, Rolando Cannalire, Francesca Esposito, Philip Gribbon, Andrea Zaliani, Daniela Iaconis, Andrea R. Beccari, Vincenzo Summa, Marcin Nowotny, Enzo Tramontano
Abstract
a small in-house library of natural compounds. Myricetin, quercetin, kaempferol, and flavanone were found to inhibit the SARS-CoV-2 nps13 unwinding activity at nanomolar concentrations, while licoflavone C was shown to block both SARS-CoV-2 nps13 activities at micromolar concentrations. Mode of action studies showed that all compounds are nsp13 noncompetitive inhibitors versus ATP, while computational studies suggested that they can bind both nucleotide and 5'-RNA nsp13 binding sites, with licoflavone C showing a unique pattern of interaction with nsp13 amino acid residues. Overall, we report for the first time natural flavonoids as selective inhibitors of SARS-CoV-2 nps13 helicase with low micromolar activity.