While not delivering a knockout blow, the discovery of penicillin in 1928 provided a potent weapon in the fight against a wide range of bacterial infections. The quest to develop a similarly broad-spectrum drug to fight viral infections has proven more difficult but now researchers at MIT's Lincoln Laboratory have designed a drug that has so far proven effective against all 15 viruses it has been tested on. These include rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever.
While there are a number drugs that are effective against specific viruses, such as the protease inhibitors used to control HIV infection, they are relatively rare and susceptible to viral resistance. In a development that could change the way viral infections are treated, the MIT researchers have designed a drug that can identify cells that have been infected not just by a specific virus, but by any virus, then kill those cells to terminate the infection.
When viruses infect a cell, they hijack its cellular machinery to create more copies of the virus, which then infect other cells, and so on. During this replication process, the viruses create long strings of double-stranded RNA (dsRNA), which isn't found in human or other animal cells. While human cells have proteins that latch onto dsRNA, which sets off a cascade of reactions that prevents the virus from replicating, many viruses are able to circumvent this by blocking one of the steps further down the cascade.
To get around this problem, Todd Rider, a senior staff scientist in Lincoln Laboratory's Chemical, Biological, and Nanoscale Technologies Group, had the idea of combining a dsRNA-binding protein with another protein that causes cells to undergo programmed cell suicide - a process called apoptosis.
The therapeutic agents devised by Rider are dubbed DRACOs (Double-stranded RNA Activated Caspase Oligomerizers). When one end of the DRACO binds to dsRNA, it signals the other end to initiate cell suicide. However, if it enters a cell and finds no dsRNA present, it leaves the cell unharmed. Because each DRACO also includes a "delivery tag," taken from naturally occurring proteins, it is able to cross cell membranes and enter any human or animal cell.
In addition to testing DRACO in human and animal cells cultured in the lab, the MIT team has also tested it in mice infected with the H1N1 influenza virus. Treated mice were completely cured of the infection and DRACO itself was shown to be not toxic to the mice. The team is now testing DRACO against more viruses in mice and reports promising results. Rider says he hopes to license the technology for trials in larger animals with his sights on eventual human clinical trials.
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