Although bacterial infections have long been treated withpenicillin, there are currently relatively few antiviral therapeutics, and mostwhich do exist are highly pathogen-specific or have other disadvantages. Butresearchers at MIT's Lincoln Laboratory are hoping to change that with thedevelopment of a drug that can identify cells that have been infected by anytype of virus, then kill those cells to terminate the infection.
The team's broad-spectrum antiviral approach, dubbedDouble-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO), selectivelyinduces apoptosis in cells containing viral dsRNA, rapidly killing infectedcells without harming uninfected cells.
MIT recently demonstrated that DRACO was effective against15 viruses—including rhinoviruses that cause the common cold, H1N1 influenza,a stomach virus, a polio virus, dengue fever and several other types ofhemorrhagic fever. These findings were published in the July 27 edition of PLoS One and present the opportunity toexplore the commercialization of a drug that effectively treats a broad classof bacterial infections, explains ToddRider, a senior staff scientist in Lincoln Laboratory's Chemical, Biological,and Nanoscale Technologies Group.
"There are very few therapeutics for viral infections, andthey tend to be highly specific for certain viruses or even certain strains ofviruses," says Rider. "For most viruses ranging from rhinovirus (the commoncold) to Ebola, there are currently no effective therapeutics. Those antiviraltherapeutics that do exist generally bind to a specific component of a specificvirus to block that virus. Because these existing drugs are so specific, it isrelatively easy for viruses to mutate and slightly change the shape of theircomponents, so that the drugs no longer bind, and the viruses become resistantto those drugs."
Rider's work is part of MIT's PANACEA project to developbroad-spectrum therapeutics. DRACO, he explains, is designed to efficientlyenter all cells in the body. If it finds viral long double-stranded RNA (dsRNA)inside cells, it immediately kills those cells by triggering apoptosis or cellsuicide, thereby rapidly terminating the viral infection. If DRACO finds noviral dsRNA inside cells, it does nothing in those cells.
"As far as is known, virtually all viruses produce longdsRNA, whereas healthy human and animal cells do not. Thus DRACO should be effectiveagainst virtually all viruses, and it should be relatively difficult forviruses to become resistant to DRACO," Rider tells ddn.
Rider and his colleagues demonstrated that DRACO wasnontoxic in all 11 cell types they have tested, including cell typesrepresenting human heart, lung, kidney, liver, etc. They also demonstrated thatDRACO was nontoxic in mice, persisted in their tissues for at least 24 to 48hours after one dose and could cure mice that had received a lethal dose ofH1N1 influenza.
The researchers will continue to test DRACO in mice, andthey hope to license the technology to pharmaceutical companies that canconduct trials in larger animals, including monkeys, then humans. MIT iscurrently entertaining possible licensing arrangements with pharmaceuticalscompanies, Rider says.
"Although more animal trials and tests against additionalviruses are needed, we believe this work has the potential to revolutionize thetreatment and prevention of a very broad range of viral diseases," he says.
The study, "Broad Spectrum Antiviral Therapeutics," wasfunded by a grant from the National Institute of Allergy and InfectiousDiseases and the New England Regional Center of Excellence for Biodefense andEmerging Infectious Diseases, with previous funding from the Defense AdvancedResearch Projects Agency, Defense Threat Reduction Agency and the director ofDefense Research & Engineering (now the Assistant Secretary of Defense forResearch and Engineering).
Rider's collaborators on the paper include Lincoln Lab staffmembers Scott Wick, Christina Zook, Tara Boettcher, Jennifer Pancoast andBenjamin Zusman.
