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.

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities / Pelliccia, S.; Wub, Y. H.; Coluccia, A.; La Regina, G.; Tseng, C. K.; Famiglini, V.; Masci, D.; Hiscott, J.; Lee, J. C.; Silvestri, R.. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - STAMPA. - 32:1(2017), pp. 1091-1101. [10.1080/14756366.2017.1355791]

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Pelliccia, S.;Coluccia, A.;La Regina, G.;Famiglini, V.;Masci, D.;Silvestri, R.
2017

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.
2017
DENV inhibitors; rdrp; NS3 protease; icr-suckling mouse; synergy
01 Pubblicazione su rivista::01a Articolo in rivista
Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities / Pelliccia, S.; Wub, Y. H.; Coluccia, A.; La Regina, G.; Tseng, C. K.; Famiglini, V.; Masci, D.; Hiscott, J.; Lee, J. C.; Silvestri, R.. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - STAMPA. - 32:1(2017), pp. 1091-1101. [10.1080/14756366.2017.1355791]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1025425
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