Premium
Design, Synthesis and Discovery of N,N’ ‐Carbazoyl‐aryl‐urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication
Author(s) -
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
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900533
Subject(s) - zika virus , aryl , virtual screening , chemistry , replication (statistics) , viral replication , virology , structure–activity relationship , drug discovery , biology , combinatorial chemistry , virus , stereochemistry , computational biology , in vitro , biochemistry , organic chemistry , alkyl
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 50 between 23–48 μM. In addition, carbazoyl‐aryl‐ureas also proved to inhibit ZIKV replication activity at micromolar concentration.