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 mM. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.
Design, synthesis and discovery of novel N,N'-carbazoyl-aryl-urea inhibitors of Zika NS5 methyltransferase and virus replication / Spizzichino, S., Mattedi, G., Lauder, K., Valle, C., Aouadi, W., Canard, B., Decroly, E., Kaptein, S., Neyts, J., Graham, C., Sule, Z., Barlow, D.j., Silvestri, R., Castagnolo, D.. - In: CHEMMEDCHEM. - ISSN 1860-7187. - 15:(2020), pp. 385-390. [10.1002/cmdc.201900533]
Design, synthesis and discovery of novel N,N'-carbazoyl-aryl-urea inhibitors of Zika NS5 methyltransferase and virus replication.
Spizzichino SPrimo
;Silvestri R;
2020
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 IC 50 between 23-48 mM. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.| File | Dimensione | Formato | |
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Note: Programma di finanziamento Horizon 2020
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