broad-spectrum antiviral therapeutics广谱抗病毒治疗.pdfVIP

Broad-Spectrum Antiviral Therapeutics Todd H. Rider*, Christina E. Zook, Tara L. Boettcher, Scott T. Wick, Jennifer S. Pancoast, Benjamin D. Zusman Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, Massachusetts, United States of America 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. Citation: Rider TH, Zook CE, Boettcher TL, Wick ST, Pancoast JS, et al. (2011) Broad-Spectrum Antiviral Therapeutics. PLoS ONE 6(7): e22572. doi:10.1371/ journal.pone.0022572 Editor: Suryaprakash Sambhara, Center for Disease Control and Prevention, United States of America Received May 20, 2011; Accepted June 24, 2011; Published July 27, 2011 Copyright: 2011 Rider et al. This is an open-access article distributed under the terms