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  • Title: Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities.
    Author: Pelliccia S, Wu YH, Coluccia A, La Regina G, Tseng CK, Famiglini V, Masci D, Hiscott J, Lee JC, Silvestri R.
    Journal: J Enzyme Inhib Med Chem; 2017 Dec; 32(1):1091-1101. PubMed ID: 28776445.
    Abstract:
    Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes - NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases.
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