Zika virus (ZIKV) infection, which initially was endemic only in Africa and Asia, is rapidly spreading throughout Europe, Oceania, and the Americas. Although there have been enormous efforts, there is still no approved drug to treat ZIKV infection. Herein, we report the synthesis and biological evaluation of agents with noncompetitive mechanism of the ZIKV NS2B/NS3 protease inhibition through the binding to an allosteric site. Compounds 1 and 2 showed potent activity in both enzymatic and cellular assays. Derivative 1 efficiently reduced the ZIKV protein synthesis and the RNA replication and prevented the mice from life-threatening infection and the brain damage caused by ZIKV infection in a ZIKV mouse model.

Discovery of Zika virus NS2B/NS3 inhibitors that prevent mice from fife-threatening infection and brain damage / Coluccia, A.; Puxeddu, M.; Nalli, M.; Wei, C. K.; Wu, Y. H.; Mastrangelo, E.; Elamin, T.; Tarantino, D.; Bugert, J. J.; Schreiner, B.; Nolte, J.; Schwarze, F.; La Regina, G.; Lee, J. C.; Silvestri, R.. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 11:10(2020), pp. 1869-1874. [10.1021/acsmedchemlett.9b00405]

Discovery of Zika virus NS2B/NS3 inhibitors that prevent mice from fife-threatening infection and brain damage

Coluccia, A.;Puxeddu, M.;Nalli, M.;La Regina, G.;Silvestri, R.
2020

Abstract

Zika virus (ZIKV) infection, which initially was endemic only in Africa and Asia, is rapidly spreading throughout Europe, Oceania, and the Americas. Although there have been enormous efforts, there is still no approved drug to treat ZIKV infection. Herein, we report the synthesis and biological evaluation of agents with noncompetitive mechanism of the ZIKV NS2B/NS3 protease inhibition through the binding to an allosteric site. Compounds 1 and 2 showed potent activity in both enzymatic and cellular assays. Derivative 1 efficiently reduced the ZIKV protein synthesis and the RNA replication and prevented the mice from life-threatening infection and the brain damage caused by ZIKV infection in a ZIKV mouse model.
2020
Zika; NS2B/NS3 protease; mouse model; modeling; synthesis
01 Pubblicazione su rivista::01a Articolo in rivista
Discovery of Zika virus NS2B/NS3 inhibitors that prevent mice from fife-threatening infection and brain damage / Coluccia, A.; Puxeddu, M.; Nalli, M.; Wei, C. K.; Wu, Y. H.; Mastrangelo, E.; Elamin, T.; Tarantino, D.; Bugert, J. J.; Schreiner, B.; Nolte, J.; Schwarze, F.; La Regina, G.; Lee, J. C.; Silvestri, R.. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 11:10(2020), pp. 1869-1874. [10.1021/acsmedchemlett.9b00405]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1436287
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