Work

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

Year: 2019

Type: article

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 μM. In addition, carbazoyl‐aryl‐ureas also proved to inhibit ZIKV replication activity at micromolar concentration.

Source: ChemMedChem

DOI: 10.1002/cmdc.201900533

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

Institutions: King's College London, Istituto Pasteur, Sapienza University of Rome, Centre National de la Recherche Scientifique, Aix-Marseille Université, Architecture et Fonction des Macromolécules Biologiques, Rega Institute for Medical Research, KU Leuven

Language: English

Topic: Mosquito-borne diseases and control

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,500

Funders: Royal Society, King's College London, Agence Nationale de la Recherche, Horizon 2020 Framework Programme, Engineering and Physical Sciences Research Council

Awards: G1053974195, Identification of viral methyltransferases inhibitors: a new antiviral strategy, G5045220161, G7429047334, G7575275224, G8465787068

OpenAlex ID: W2994315817

FWCI: 2.532

Cites: 28

Cited by: 26

Related to: 10