DRACO Down the Memory Hole

They had a cure over a decade ago, but not for you.

Double-stranded RNA Activated Caspase Oligomerizer

On July 27th, 2011, a paper was published in PLOS ONE describing a novel protein biologic antiviral. It was called DRACO, an acronym for Double-stranded RNA Activated Caspase Oligomerizer.

PLOS - Broad-Spectrum Antiviral Therapeutics

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.

Funding: This work is funded by grant AI057159 (http://www.niaid.nih.gov/Pages/default.aspx) from the National Institute of Allergy and Infectious Diseases and the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, with previous funding from the Defense Advanced Research Projects Agency, Defense Threat Reduction Agency, and Director of Defense Research & Engineering. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the United States government.

This research was performed at MIT’s Draper Labs and was funded by NIAID, DARPA, and DTRA. The Pentagon were after a broad-spectrum antivirus that could cure any viral infection, in case soldiers were exposed to an unknown pathogen for which no vaccine existed (i.e. a biowarfare agent). Dr. Todd Rider’s solution was to come up with a chimeric protein consisting of a dsRNA detection domain fused end-to-end with an apoptosis induction domain. These protein biologics were produced by being cultured in a bioreactor in E. Coli bacteria transfected with plasmids to produce DRACO proteins, similar to how recombinant insulin is produced.

It is possible to formulate different types of DRACOs, such as Protein Kinase R and Apoptotic protease activating factor-1, PKR and FADD, RNaseL and Apaf-1, et cetera. DRACOs all have the same mechanism of action. They take advantage of the fact that many viruses, including coronaviruses, produce long strands of dsRNA when they infect cells and replicate. Even viruses with ssRNA genomes like SARS-CoV-2 do this. Healthy cells, on the other hand, don’t have any dsRNA in them at all.