Your browser doesn't support javascript.
Natural Compounds Inhibit SARS-CoV-2 nsp13 Unwinding and ATPase Enzyme Activities.
Corona, Angela; Wycisk, Krzysztof; Talarico, Carmine; Manelfi, Candida; Milia, Jessica; Cannalire, Rolando; Esposito, Francesca; Gribbon, Philip; Zaliani, Andrea; Iaconis, Daniela; Beccari, Andrea R; Summa, Vincenzo; Nowotny, Marcin; Tramontano, Enzo.
  • Corona A; Dipartimento di Scienze della vita e dell'ambiente, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, SS-554, 09042 Monserrato, Cagliari, Italy.
  • Wycisk K; Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Ks. Trojdena 4, Warsaw 02-109, Poland.
  • Talarico C; Dompé Farmaceutici SpA, via Campo di Pile, 67100 L'Aquila, Italy.
  • Manelfi C; Dompé Farmaceutici SpA, via Campo di Pile, 67100 L'Aquila, Italy.
  • Milia J; Dipartimento di Scienze della vita e dell'ambiente, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, SS-554, 09042 Monserrato, Cagliari, Italy.
  • Cannalire R; Department of Pharmacy, University of Napoli "Federico II", via D. Montesano 49, Napoli 80131, Italy.
  • Esposito F; Dipartimento di Scienze della vita e dell'ambiente, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, SS-554, 09042 Monserrato, Cagliari, Italy.
  • Gribbon P; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.
  • Zaliani A; Fraunhofer Cluster of Excellence for Immune Mediated Diseases (CIMD), Theodor Stern Kai 7, 60590 Frankfurt, Germany.
  • Iaconis D; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.
  • Beccari AR; Fraunhofer Cluster of Excellence for Immune Mediated Diseases (CIMD), Theodor Stern Kai 7, 60590 Frankfurt, Germany.
  • Summa V; Dompé Farmaceutici SpA, via Campo di Pile, 67100 L'Aquila, Italy.
  • Nowotny M; Dompé Farmaceutici SpA, via Campo di Pile, 67100 L'Aquila, Italy.
  • Tramontano E; Department of Pharmacy, University of Napoli "Federico II", via D. Montesano 49, Napoli 80131, Italy.
ACS Pharmacol Transl Sci ; 5(4): 226-239, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1852382
ABSTRACT
SARS-CoV-2 infection is still spreading worldwide, and new antiviral therapies are an urgent need to complement the approved vaccine preparations. SARS-CoV-2 nps13 helicase is a validated drug target participating in the viral replication complex and possessing two associated activities RNA unwinding and 5'-triphosphatase. In the search of SARS-CoV-2 direct antiviral agents, we established biochemical assays for both SARS-CoV-2 nps13-associated enzyme activities and screened both in silico and in vitro 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.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Vaccines Language: English Journal: ACS Pharmacol Transl Sci Year: 2022 Document Type: Article Affiliation country: Acsptsci.1c00253

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Vaccines Language: English Journal: ACS Pharmacol Transl Sci Year: 2022 Document Type: Article Affiliation country: Acsptsci.1c00253