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Many Viruses Stopped by New Kind of Drug

Background

Doctors use antibiotics like penicillin and erythromycin to treat bacterial infections, but these drugs are useless against viruses. There are antiviral drugs to treat certain viruses, such as HIV and hepatitis, but there are very few broadly effective treatments that can take on an array of viruses.

Results

A scientist working at a microscope
Dr. Todd Rider of the Massachusetts Institute of Technology (MIT) working in his laboratory. Courtesy: MIT.

In July 2011, researchers supported by NIAID’s New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases reported promising early results with a compound they invented called DRACO (Double-stranded RNA Activated Caspase Oligomerizer). In lab-grown cells, DRACO killed 15 different viruses, including ones that cause the common cold, influenza, polio and dengue fever.

DRACO combines two naturally occurring cell defense proteins into a single compound that delivers a one-two knock-out punch to virus-infected cells, while sparing healthy ones. First, DRACO detects long, double-stranded RNA chains that are made by viruses when they replicate inside an infected cell. Uninfected cells do not have such long chains, so DRACO has no effect on them.

After binding to viral double-stranded RNA, the second DRACO protein prompts the cell to self-destruct. This self-destruct protein also occurs naturally, but the cellular signals that trigger it are often blocked by the infecting virus. In effect, DRACO attacks viruses in a way that is not seen in nature. This means that viruses have not had the opportunity to evolve defenses against this kind of attack.

Todd Rider, Ph.D., of the Massachusetts Institute of Technology, led the research, which was published in the journal PLoS ONE in July 2011.

In addition to testing DRACO on lab-grown cells, Dr. Rider and his colleagues also used the compound to successfully treat mice infected with a lethal dose of H1N1 influenza virus.

Significance

Existing antiviral drugs are few in number and are generally directed at a single viral disease. Through rapid mutation, viruses tend to become resistant to single drugs that target some specific viral component. Unlike other antiviral drugs, DRACO detects a process—the production of double-stranded RNA—that almost all viruses use. Dr. Rider’s team has already shown that viruses with double-stranded RNA, single-stranded RNA, and DNA genomes all produce double-stranded RNA and can be successfully treated with DRACO. Because DRACO combines double-stranded RNA detection with a protein that causes the infected cell to self-destruct, viruses will have little opportunity to develop resistance to it.

Next Steps

Next steps for the researchers will include testing DRACO against additional viruses and in other, larger animals with aims of verifying its safety and improving its activity. If results are promising, the compound could eventually be tested in human clinical trials.

Reference

TH Rider et al. Broad-spectrum antiviral therapeutics. PLoS ONE. DOI:10.1371/journal.pone.0022572 (2011).

Slides of treated and untreated rhinovirus and dengue, both infected and not infected.
Left (yellow) photos: DRACO cures human cells infected with rhinovirus, the common cold virus, with no toxicity. Scale bar = 50 micrometers. Right (orange/red) photos: DRACO cures monkey cells infected with dengue homorrhagic fever virus, with no toxicity. Scale bar = 100 micrometers. Credit: NIAID

Last Updated October 07, 2011

Last Reviewed September 19, 2011