Articles
VIRTUAL SCREENING APPROACH FOR THE IDENTIFICATION OF POTENTIAL CITRUS TRISTEZA VIRUS INHIBITORS
Article number
892_30
Pages
257 – 264
Language
English
Abstract
Citrus tristeza virus (CTV) causes a most destructive citrus disease and several approaches have been implemented to control damages as eradication programs, use of tolerant or resistant rootstocks and cross protection.
The aim of this study was the identification of molecules interfering with CTV replication, by GriDock, a molecular modelling software, developed to identify potentially bioactive compounds (hit-compounds). It’s based on the virtual-screening approach in which the activity of a large set of molecules is predicted by multiple molecular docking calculations.
With a view to verify its potentialities, the RdRp (RNA dependent RNA polymerase) enzyme was considered as potential therapeutic target for citrus infected by CTV and its 3D structure was obtained through homology approaches.
The screening of more than one million of molecules allowed the identification of several potential RdRp inhibitors.
We have chosen a sulfonic acid and a penicillin derivative and tested their effect on CTV replication in vitro by a quantitative real-time PCR assay.
The results showed that the selected drugs were able to reduce virus replication rate in a range between 40 and 82%. The achieved results must be considered preliminary, but they appear a good starting point to develop a drug class against CTV infections.
The aim of this study was the identification of molecules interfering with CTV replication, by GriDock, a molecular modelling software, developed to identify potentially bioactive compounds (hit-compounds). It’s based on the virtual-screening approach in which the activity of a large set of molecules is predicted by multiple molecular docking calculations.
With a view to verify its potentialities, the RdRp (RNA dependent RNA polymerase) enzyme was considered as potential therapeutic target for citrus infected by CTV and its 3D structure was obtained through homology approaches.
The screening of more than one million of molecules allowed the identification of several potential RdRp inhibitors.
We have chosen a sulfonic acid and a penicillin derivative and tested their effect on CTV replication in vitro by a quantitative real-time PCR assay.
The results showed that the selected drugs were able to reduce virus replication rate in a range between 40 and 82%. The achieved results must be considered preliminary, but they appear a good starting point to develop a drug class against CTV infections.
Authors
A. Lombardo, G. Licciardello, A. Bertuccio, G. Vistoli, A. Pedretti
Keywords
CTV, drug discovery, RdRp, molecular docking, Real-time PCR, molecular modelling
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