Broad-spectrum antiviral therapeutics
Todd H Rider, Christina E Zook, Tara L Boettcher, Scott T Wick, Jennifer S Pancoast, Benjamin D Zusman, Todd H Rider, Christina E Zook, Tara L Boettcher, Scott T Wick, Jennifer S Pancoast, Benjamin D Zusman
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.
Conflict of interest statement
Competing Interests: THR is the inventor on patents and patent applications covering DRACOs: Rider TH (issued October 24, 2006) Anti-pathogen treatments. U.S. Patent 7,125,839; Rider TH (issued July 28, 2009) Anti-pathogen treatments. U.S. Patent 7,566,694; Rider TH (filed June 18, 2009) Anti-Pathogen Treatments. U.S. Patent Application 20100098680; Rider TH (filed February 7, 2003) Anti-Pathogen Treatments. European Patent Application 03716001.7; Rider TH (filed February 7, 2003) Anti-Pathogen Treatments. Canadian Patent Application 2,475,247; Rider TH (filed February 7, 2003) Anti-Pathogen Treatments. Patent Cooperation Treaty Serial No. US03/03978; Rider TH (filed February 7, 2003) Anti-Pathogen Treatments. Japanese Patent Application 2003565429; Rider TH (filed November 19, 2009) Anti-Pathogen Treatments. Japanese Patent Application 2009262426. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
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Source: PubMed