Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
08 Jul 2021
08 Jul 2021
Historique:
received:
11
03
2021
accepted:
08
06
2021
entrez:
14
7
2021
pubmed:
15
7
2021
medline:
15
7
2021
Statut:
epublish
Résumé
Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the inhibitory activity of the synthesized compounds showed nanomolar to submicromolar IC
Identifiants
pubmed: 34257831
doi: 10.1021/acsmedchemlett.1c00140
pmc: PMC8204913
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1102-1107Informations de copyright
© 2021 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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