Broad spectrum anti-flavivirus pyridobenzothiazolones leading to less infective virions.

Authors:
Rolando Cannalire
Rolando Cannalire
Università degli Studi di Perugia
Peru
Delia Tarantino
Delia Tarantino
Università degli Studi di Milano
Italy
Geraldine Piorkowski
Geraldine Piorkowski
Aix Marseille Université
Marseille | France
Tea Carletti
Tea Carletti
Uppsala University
Sweden
Serena Massari
Serena Massari
Università di Perugia
Peru
Tommaso Felicetti
Tommaso Felicetti
University of Perugia
Perugia | Italy
Maria Letizia Barreca
Maria Letizia Barreca
Università di Messina
Italy
Stefano Sabatini
Stefano Sabatini
Università degli Studi di Perugia

Antiviral Res 2019 Jul 6;167:6-12. Epub 2019 Mar 6.

UMR "Emergence des Pathologies Virales" (Aix-Marseille University - IRD 190 - Inserm 1207 - EHESP), Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Faculté de Médecine, 27 bd Jean Moulin, 13005 Marseille, France. Electronic address:

We report the design, synthesis, and biological evaluation of a class of 1H-pyrido[2,1-b][1,3]benzothiazol-1-ones originated from compound 1, previously identified as anti-flavivirus agent. Some of the new compounds showed activity in low μM range with reasonable selectivity against Dengue 2, Yellow fever (Bolivia strain), and West Nile viruses. One of the most interesting molecules, compound 16, showed broad antiviral activity against additional flaviviruses such as Dengue 1, 3 and 4, Zika, Japanese encephalitis, several strains of Yellow fever, and tick-borne encephalitis viruses. Compound 16 did not exert any effect on alphaviruses and phleboviruses and its activity was maintained in YFV infected cells from different species. The activity of 16 appears specific for flavivirus with respect to other virus families, suggesting, but not proving, that it might be targeting a viral factor. We demonstrated that the antiviral effect of 16 is not related to reduced viral RNA synthesis or virion release. On the contrary, viral particles grown in the presence of 16 showed reduced infectivity, being unable to perform a second round of infection. The chemical class herein presented thus emerges as suitable to provide pan-flavivirus inhibitors.

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http://dx.doi.org/10.1016/j.antiviral.2019.03.004DOI Listing
July 2019
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