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A Novel Agonist of the TRIF Pathway Induces a Cellular State Refractory to Replication of Zika, Chikungunya, and Dengue Viruses

2017; American Society for Microbiology; Volume: 8; Issue: 3 Linguagem: Inglês

10.1128/mbio.00452-17

2161-2129

Kara Pryke, Jinu Abraham, Tina M. Sali, Bryan Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason R. Baird, Michael J. Gough, Marita Chakhtoura, Elias K. Haddad, Ilsa T. Kirby, Aaron Nilsen, Daniel N. Streblow, Alec J. Hirsch, Jessica L. Smith, Victor R. DeFilippis,

Viral Infections and Vectors

The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread. In light of this strategy's potential, we undertook a screen to identify novel interferon-activating small molecules. Here, we describe 1-(2-fluorophenyl)-2-(5-isopropyl-1,3,4-thiadiazol-2-yl)-1,2-dihydrochromeno[2,3-