PANACEA broad-spectrum antiviral therapeutics was presented at Strategies for Engineering Negligible Senescence SENS-6.
Although there is great concern over emerging viruses and viruses on the category A-C priority pathogen lists, there are relatively few prophylactics or therapeutics for these viruses, and most which do exist are highly pathogen-specific or have undesirable side effects or other disadvantages. As part of our PANACEA program, we have developed a radically new and very broad-spectrum antiviral therapeutic/prophylactic that has the potential to revolutionize the treatment of viral infections, including those due to emerging, category A-C, and common clinical pathogens. Our Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) approach selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have demonstrated that DRACOs are nontoxic in all 11 cell types tested thus far, and effective against 15 different viruses, including DNA and RNA viruses, enveloped and nonenveloped viruses, viruses that replicate in the nucleus and in the cytoplasm, and viruses that use a variety of receptors. Among the viruses against which DRACOs have proven effective in vitro are dengue hemorrhagic fever virus, multiple arenaviruses, and multiple bunyaviruses. In mice, we have demonstrated that DRACOs rapidly penetrate into all organs tested, persist for over 24 hours after each dose, and are nontoxic. We have shown that DRACOs rescue mice from lethal challenges with H1N1 influenza, Tacaribe arenavirus, Amapari arenavirus, and Guama bunyavirus. We hope to optimize our DRACO designs and demonstrate them against additional viruses and in additional animal models. This work should greatly advance DRACOs toward ultimate utility as safe, broad-spectrum therapeutics/prophylactics for priority and emerging viral pathogens, filling a large gap in existing therapeutics.