Experimental Drug Could Defeat Any Virus
Interesting article from my favorite news site, New Scientist. I post a lot of articles from there, so check back periodically or check out the site yourself.
Viruses might soon meet their kryptonite: an experimental drug that can, in theory, obliterate cells infected by any type of virus without harming healthy neighbours.
For 50 years, we have been fighting viruses in two ways: drugs for existing infections and vaccines to prevent infection in the first place. However, most drugs or vaccines are specific to one virus, viral strain or family of related viruses. When a virus mutates – as they so often do – researchers must retool our medicines.
The new drug targets a molecule common to all virus-infected cells. Nearly every virus generates strings of double-stranded RNA longer than 30 base pairs during transcription and replication, in an attempt to duplicate itself and commandeer its host cell's machinery. Healthy mammalian cells do not produce double-stranded RNA longer than 23 base pairs.
The immune artillery within mammalian cells includes a protein that exploits this viral characteristic. Todd Rider of the Massachusetts Institute of Technology's Lincoln Laboratory in Lexington, Massachusetts, and his colleagues combined this protein with another from the immune system to produce their new drug.
When a sentinel enzyme called protein kinase R (PKR) finds double-stranded RNA longer than 23 base pairs inside a cell, it binds to the RNA, blocks the production of viral proteins and activates the cell's defences. Many viruses, though, have evolved ways to evade PKR.
Unleash the enzymes
So Rider and his colleagues glued PKR to apoptotic protease activating factor 1 (APAF-1), a protein that triggers cell suicide by unleashing a team of destructive enzymes. Healthy cells normally reserve APAF-1 for extreme situations – to trigger self-destruction in a cancerous cell, for instance – but as part of the new antiviral drug, APAF-1 is activated as soon as PKR identifies and binds to lengthy molecules of double-stranded RNA in an infected cell.
The drug "catches the virus with its pants down", by destroying the cell before new viruses have been assembled inside it, explains Rider. Even if fragmented virus molecules escape the obliterated cell, they will be missing the protein coat that helps them to travel between cells, and so will not infect surrounding healthy tissue. Rider calls his drug double-stranded RNA (dsRNA)-activated caspase oligomeriser (DRACO).
In tests, Rider infected human and mouse cells in Petri dishes with rhinovirus, which causes some forms of the common cold in humans. DRACO prevented the virus from spreading by rapidly killing infected cells without harming healthy ones. Further tests showed that DRACO performs just as well against 14 other viruses, including the one responsible for dengue fever. It also helped boost survival rates in mice given an otherwise lethal dose of the H1N1 flu virus.
"Just as antibiotics revolutionised the treatment of bacterial infections, this project has a lot of potential to prevent or treat a whole range of infectious illnesses," says Rider. Infections on the hit list range from "the common cold to quite serious diseases – [and] even [the most] drug-resistant HIV", he says. DRACO could also act a shield against viruses that might appeal to bioterrorists, such as Ebola and smallpox.
Andrea Branch of the Mount Sinai School of Medicine in New York City thinks the work is intriguing but has some reservations about its practicality. She points out that DRACO is a large protein, which may not enter cells easily.
That said, she agrees that administering DRACO early in an infection could be effective – but adds that destroying all cells infected with the virus can be dangerous in people with advanced viral infections. "Suppose 100 per cent of your hepatocytes [liver cells] are infected and you used this – you would die of liver failure."
Timothy Tellinghuisen of the Scripps Research Institute in Jupiter, Florida, adds that some viruses have evolved ways to conceal their double-stranded RNA, and so could elude DRACO. Still, "this is really an interesting paper, a very clever approach to getting rid of cells containing double-stranded RNA", he says.
Journal reference: PLoS One, DOI: 10.1371/journal.pone.0022572