Development of novel strategies to fight flaviviruses: from targeted screen to in vivo antiviral validation

Séminaires
Date: vendredi 14 décembre 2018 11:00

Lieu: Marcel Dorée Seminar Room  |  Ville: Montpellier, France

Abstract:

The increasing prevalence of Dengue virus (DENV) worldwide heightens the need for an effective vaccine and/or antiviral. Current DENV vaccination campaign are controversial and no efficient antiviral treatment has been approved yet. Classical antiviral approaches involve design of drugs that directly target viral proteins; this approach being challenging due to the intrinsically high mutation rate of RNA virus polymerases leading to antiviral resistance. Thus, our work aims at discovering novel host-targeted antiviral compounds active against flaviviruses. The presentation will discuss advances in the identification and characterization of two highly potent antiviral molecules. I will describe the screening strategy, the improvement of the drug through structure-activity-relationship (SAR), the identification of the viral cycle step inhibited and the in vivo validation of one of the compounds.

References:

de Wispelaere M, Carocci M, Liang Y, Liu Q, Sun E, Vetter ML, Wang J, Gray NS, Yang PL. Discovery of host-targeted covalent inhibitors of dengue virus. Antiviral Research 2017.

Liang Y*, de Wispelaere M*, Carocci M*, Liu Q, Wang J, Yang PL, Gray NS. Structure-Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent. ACS Medical Chemistry Letter 2017.

Carocci M, Hinshaw S, Rodgers MA, Villareal V, Burri DJ, Pilenkatta R, Maharaj N, Gack MU, Stavale EJ, Warfield KL and Yang PL. The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication. Antiviral Agent & Chemotherapy, 2015.

 

Margot Gaudin Carocci, PhD

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  • vendredi 14 décembre 2018 11:00
 

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