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

ABSTRACT: 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 IC50 between 23-48??M. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.

SUBMITTER: Spizzichino S

PROVIDER: S-EPMC7106487 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Spizzichino Sharon S Mattedi Giulio G Lauder Kate K Valle Coralie C Aouadi Wahiba W Canard Bruno B Decroly Etienne E Kaptein Suzanne J F SJF Neyts Johan J Graham Carl C Sule Zakary Z Barlow David J DJ Silvestri Romano R Castagnolo Daniele D

ChemMedChem 20200107 4

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<sub>50</sub> between 23-48 μM. I ...[more]

PMID: 31805205

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