Identification and evaluation of potential SARS-CoV-2 antiviral agents targeting mRNA cap guanine N7-Methyltransferase.

Antiviral Agents / chemistry COVID-19 / virology Cell Line Exoribonucleases / antagonists & inhibitors High-Throughput Screening Assays Humans Inhibitory Concentration 50 Methyltransferases / antagonists & inhibitors Nucleotidyltransferases / antagonists & inhibitors RNA Caps RNA, Viral / genetics SARS-CoV-2 / drug effects Viral Nonstructural Proteins / antagonists & inhibitors Virus Replication / drug effects COVID-19 Drug Treatment
COVID-19 Fluorescence assay Inhibitor screening nsp14

Journal

Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699

Informations de publication

Date de publication:
09 2021
Historique:
received: 28 04 2021
revised: 25 06 2021
accepted: 19 07 2021
pubmed: 26 7 2021
medline: 19 8 2021
entrez: 25 7 2021
Statut: ppublish

Résumé

SARS-CoV-2, the cause of the currently ongoing COVID-19 pandemic, encodes its own mRNA capping machinery. Insights into this capping system may provide new ideas for therapeutic interventions and drug discovery. In this work, we employ a previously developed Py-FLINT screening approach to study the inhibitory effects of compounds against the cap guanine N7-methyltransferase enzyme, which is involved in SARS-CoV-2 mRNA capping. We screened five commercially available libraries (7039 compounds in total) to identify 83 inhibitors with IC

Identifiants

DOI: 10.1016/j.antiviral.2021.105142 PMID: 34303749 PMC: PMC8299157
pubmed: 34303749
pii: S0166-3542(21)00132-7
doi: 10.1016/j.antiviral.2021.105142
pmc: PMC8299157
pii:
doi:

Substances chimiques

Antiviral Agents 0
RNA Caps 0
RNA, Viral 0
Viral Nonstructural Proteins 0
Methyltransferases EC 2.1.1.-
mRNA (guanine(N7))-methyltransferase EC 2.1.1.56
Nucleotidyltransferases EC 2.7.7.-
mRNA guanylyltransferase EC 2.7.7.50
Exoribonucleases EC 3.1.-
NSP14 protein, SARS-CoV-2 EC 3.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

105142

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

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Auteurs

Renata Kasprzyk (R)

Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland; College of Inter-Faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland.

Tomasz J Spiewla (TJ)

Division of Biophysics, Faculty of Physics, University of Warsaw, Pasteura 5, 02-093, Warsaw, Poland; Explorna Therapeutics sp. z o.o, Zwirki i Wigury 101/0.30, 02-089, Warsaw, Poland.

Miroslaw Smietanski (M)

Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland.

Sebastian Golojuch (S)

Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland; Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093, Warsaw, Poland.

Laura Vangeel (L)

KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, 3000, Leuven, Belgium.

Steven De Jonghe (S)

KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, 3000, Leuven, Belgium.

Dirk Jochmans (D)

KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, 3000, Leuven, Belgium.

Johan Neyts (J)

KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, 3000, Leuven, Belgium.

Joanna Kowalska (J)

Division of Biophysics, Faculty of Physics, University of Warsaw, Pasteura 5, 02-093, Warsaw, Poland. Electronic address: Joanna.Kowalska@fuw.edu.pl.

Jacek Jemielity (J)

Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland. Electronic address: j.jemielity@cent.uw.edu.pl.

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