title: Broad-spectrum antiviral therapeutics.
abstract: Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.
authors.affiliation: Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, Massachusetts, United States of America. thor@LL.MIT.EDU
authors.forename: Todd H
authors.initials: TH
authors.lastname: Rider
authors.forename: Christina E
authors.initials: CE
authors.lastname: Zook
authors.forename: Tara L
authors.initials: TL
authors.lastname: Boettcher
authors.forename: Scott T
authors.initials: ST
authors.lastname: Wick
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Pancoast
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Zusman
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000821:virology; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D012330:RNA, Double-Stranded / Q000378:metabolism; D014780:Viruses / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D012330:RNA, Double-Stranded; D020169:Caspases