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Design, Synthesis and Discovery of N,N’-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication

ChemMedChem, ISSN: 1860-7187, Vol: 15, Issue: 4, Page: 385-390
2020
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Article Description

The recent outbreaks of Zika virus (ZIKV) infection worldwide make the discovery of novel antivirals against flaviviruses a research priority. This work describes the identification of novel inhibitors of ZIKV through a structure-based virtual screening approach using the ZIKV NS5-MTase. A novel series of molecules with a carbazoyl-aryl-urea structure has been discovered and a library of analogues has been synthesized. The new compounds inhibit ZIKV MTase with IC between 23–48 μM. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.

Bibliographic Details

Spizzichino, Sharon; Mattedi, Giulio; Lauder, Kate; Valle, Coralie; Aouadi, Wahiba; Canard, Bruno; Decroly, Etienne; Kaptein, Suzanne J F; Neyts, Johan; Graham, Carl; Sule, Zakary; Barlow, David J; Silvestri, Romano; Castagnolo, Daniele

Wiley

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Chemistry

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