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August 10, 2011

New drug could cure nearly any viral infection including the common cold, SARS and flu

a team of researchers at MIT’s Lincoln Laboratory has designed a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.

Researchers at MIT’s Lincoln Lab have developed technology that may someday cure the common cold, influenza and other ailments. A team of researchers at MIT’s Lincoln Laboratory has designed a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.

The researchers tested their drug against 15 viruses, and found it was effective against all of them — including rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever.

PLos ONE - 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.

Rider had the idea to combine a dsRNA-binding protein with another protein that induces cells to undergo apoptosis (programmed cell suicide) — launched, for example, when a cell determines it is en route to becoming cancerous. Therefore, when one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to initiate cell suicide.

Combining those two elements is a “great idea” and a very novel approach, says Karla Kirkegaard, professor of microbiology and immunology at Stanford University. “Viruses are pretty good at developing resistance to things we try against them, but in this case, it’s hard to think of a simple pathway to drug resistance,” she says.

Each DRACO also includes a “delivery tag,” taken from naturally occurring proteins, that allows it to cross cell membranes and enter any human or animal cell. However, if no dsRNA is present, DRACO leaves the cell unharmed.

Most of the tests reported in this study were done in human and animal cells cultured in the lab, but the researchers also tested DRACO in mice infected with the H1N1 influenza virus. When mice were treated with DRACO, they were completely cured of the infection. The tests also showed that DRACO itself is not toxic to mice.

The researchers are now testing DRACO against more viruses in mice and beginning to get promising results. Rider says he hopes to license the technology for trials in larger animals and for eventual human clinical trials.

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