CAMBRIDGE, Mass.—Scientists at the Massachusetts Institute of Technology (MIT) have designed a drug that could effectively treat the common cold, influenza and even deadly hemorrhagic fevers such as Ebola—filling a gaping hole in modern medicine's ability to treat people with viral infections.
Although bacterial infections have long been treated with penicillin, there are currently relatively few antiviral therapeutics, and most that do exist are highly pathogen-specific or have other disadvantages. But researchers at MIT's Lincoln Laboratory are hoping to change that with the development of a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.
The team's broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO), selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells.
MIT recently demonstrated that DRACO was effective against 15 viruses—including rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever. These findings were published in the July 27 edition of PLoS One and present the opportunity to explore the commercialization of a drug that effectively treats a broad class of bacterial infections, explains Todd Rider, a senior staff scientist in Lincoln Laboratory's Chemical, Biological and Nanoscale Technologies Group.
"There are very few therapeutics for viral infections, and they tend to be highly specific for certain viruses or even certain strains of viruses," says Rider. "For most viruses ranging from rhinovirus (the common cold) to Ebola, there are currently no effective therapeutics. Those antiviral therapeutics that do exist generally bind to a specific component of a specific virus to block that virus. Because these existing drugs are so specific, it is relatively easy for viruses to mutate and slightly change the shape of their components, so that the drugs no longer bind, and the viruses become resistant to those drugs."
Rider's work is part of MIT's PANACEA project to develop broad-spectrum therapeutics. DRACO, he explains, is designed to efficiently enter all cells in the body. If it finds viral long double-stranded RNA inside cells, it immediately kills those cells by triggering apoptosis or cell suicide, thereby rapidly terminating the viral infection. If DRACO finds no viral dsRNA inside cells, it does nothing in those cells.
"As far as is known, virtually all viruses produce long dsRNA, whereas healthy human and animal cells do not. Thus DRACO should be effective against virtually all viruses, and it should be relatively difficult for viruses to become resistant to DRACO," Rider tells ddn. Rider and his colleagues demonstrated that DRACO was nontoxic in all 11 cell types they have tested, including cell types representing human heart, lung, kidney, liver, etc. They also demonstrated that DRACO was nontoxic in mice, persisted in their tissues for at least 24 to 48 hours after one dose and could cure mice that had received a lethal dose of H1N1 influenza.
The researchers will continue to test DRACO in mice, and they hope to license the technology to pharmaceutical companies that can conduct trials in larger animals, including monkeys, then humans. MIT is currently entertaining possible licensing arrangements with pharmaceuticals companies, Rider says.
"Although more animal trials and tests against additional viruses are needed, we believe this work has the potential to revolutionize the treatment and prevention of a very broad range of viral diseases," he says.
The study, "Broad Spectrum Antiviral Therapeutics," was funded by a grant 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 the director of Defense Research & Engineering (now the Assistant Secretary of Defense for Research and Engineering).
Rider's collaborators on the paper include Lincoln Lab staff members Scott Wick, Christina Zook, Tara Boettcher, Jennifer Pancoast and Benjamin Zusman.
