Probing the SAM Binding Site of SARS-CoV-2 Nsp14 In Vitro Using SAM Competitive Inhibitors Guides Developing Selective Bisubstrate Inhibitors.

Antiviral Agents / pharmacology Binding Sites / genetics COVID-19 / genetics Exoribonucleases / genetics Humans Methylation Pandemics Protein Binding / genetics RNA, Viral / genetics SARS-CoV-2 / genetics Viral Nonstructural Proteins / genetics Virus Replication / genetics
COVID-19 SARS-CoV-2 coronavirus nsp14

Journal

SLAS discovery : advancing life sciences R & D
ISSN: 2472-5560
Titre abrégé: SLAS Discov
Pays: United States
ID NLM: 101697563

Informations de publication

Date de publication:
10 2021
Historique:
pubmed: 2 7 2021
medline: 29 9 2021
entrez: 1 7 2021
Statut: ppublish

Résumé

The COVID-19 pandemic has clearly brought the healthcare systems worldwide to a breaking point, along with devastating socioeconomic consequences. The SARS-CoV-2 virus, which causes the disease, uses RNA capping to evade the human immune system. Nonstructural protein (nsp) 14 is one of the 16 nsps in SARS-CoV-2 and catalyzes the methylation of the viral RNA at N7-guanosine in the cap formation process. To discover small-molecule inhibitors of nsp14 methyltransferase (MTase) activity, we developed and employed a radiometric MTase assay to screen a library of 161 in-house synthesized

Identifiants

DOI: 10.1177/24725552211026261 PMID: 34192965 PMC: PMC8458670
pubmed: 34192965
doi: 10.1177/24725552211026261
pmc: PMC8458670
pii: S2472-5552(22)06758-2
doi:

Substances chimiques

Antiviral Agents 0
RNA, Viral 0
Viral Nonstructural Proteins 0
Exoribonucleases EC 3.1.-
NSP14 protein, SARS-CoV-2 EC 3.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1200-1211

Subventions

Organisme : Wellcome Trust
ID : 106169/ZZ14/Z
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : HHSN272201700060C
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM131858
Pays : United States

Commentaires et corrections

Type : UpdateOf

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Auteurs

Kanchan Devkota (K)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Matthieu Schapira (M)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.

Sumera Perveen (S)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Aliakbar Khalili Yazdi (A)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Fengling Li (F)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Irene Chau (I)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Pegah Ghiabi (P)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Taraneh Hajian (T)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Peter Loppnau (P)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Albina Bolotokova (A)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Karla J F Satchell (KJF)

Department of Microbiology-Immunology, Northwestern University, Center for Structural Genomics of Infectious Diseases, Feinberg School of Medicine, Chicago, IL, USA.

Ke Wang (K)

Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Program of Pharmacology, Weill Cornell Medical College of Cornell University, New York, NY, USA.

Deyao Li (D)

Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Program of Pharmacology, Weill Cornell Medical College of Cornell University, New York, NY, USA.

Jing Liu (J)

Departments of Pharmacological Sciences and Oncological Sciences, Mount Sinai Center for Therapeutics Discovery, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

David Smil (D)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Minkui Luo (M)

Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Program of Pharmacology, Weill Cornell Medical College of Cornell University, New York, NY, USA.

Jian Jin (J)

Departments of Pharmacological Sciences and Oncological Sciences, Mount Sinai Center for Therapeutics Discovery, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Paul V Fish (PV)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, London, UK.

Peter J Brown (PJ)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.

Masoud Vedadi (M)

Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0002-0574-0169

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Ribonucléases › Exoribonucleases › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Métabolisme › Alkylation › Méthylation › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Épidémies de maladies › Épidémies › Pandémies › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN viral › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales non structurales › Probing the SAM Binding Site of SARS-CoV-2...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Probing the SAM Binding Site of SARS-CoV-2...