Could New Drug Cure Nearly Any Viral Infection? Technology Shows Promise Against Common Cold, Influenza and Other Ailments, Researchers Say

[Guest guest]

http://www.sciencedaily.com/releases/2011/08/110826134012.htm

Could New Drug Cure Nearly Any Viral Infection? Technology Shows Promise Against

Common Cold, Influenza and Other Ailments, Researchers Say

ScienceDaily (Aug. 26, 2011) — Most bacterial infections can be treated with

antibiotics such as penicillin, discovered decades ago. However, such drugs are

useless against viral infections, including influenza, the common cold, and

deadly hemorrhagic fevers such as Ebola.

Now, in a development that could transform how viral infections are treated, 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.

In a paper published July 27 in the journal PLoS ONE, 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.

The drug works by targeting a type of RNA produced only in cells that have been

infected by viruses. " In theory, it should work against all viruses, " says Todd

Rider, a senior staff scientist in Lincoln Laboratory's Chemical, Biological,

and Nanoscale Technologies Group who invented the new technology.

Because the technology is so broad-spectrum, it could potentially also be used

to combat outbreaks of new viruses, such as the 2003 SARS (severe acute

respiratory syndrome) outbreak, Rider says.

Other members of the research team are Lincoln Lab staff members Wick,

Zook, Tara Boettcher, Pancoast and Zusman.

Few antivirals available

Rider had the idea to try developing a broad-spectrum antiviral therapy about 11

years ago, after inventing CANARY (Cellular Analysis and Notification of Antigen

Risks and Yields), a biosensor that can rapidly identify pathogens. " If you

detect a pathogenic bacterium in the environment, there is probably an

antibiotic that could be used to treat someone exposed to that, but I realized

there are very few treatments out there for viruses, " he says.

There are a handful of drugs that combat specific viruses, such as the protease

inhibitors used to control HIV infection, but these are relatively few in number

and susceptible to viral resistance.

Rider drew inspiration for his therapeutic agents, dubbed DRACOs

(Double-stranded RNA Activated Caspase Oligomerizers), from living cells' own

defense systems.

When viruses infect a cell, they take over its cellular machinery for their own

purpose -- that is, creating more copies of the virus. During this process, the

viruses create long strings of double-stranded RNA (dsRNA), which is not found

in human or other animal cells.

As part of their natural defenses against viral infection, human cells have

proteins that latch onto dsRNA, setting off a cascade of reactions that prevents

the virus from replicating itself. However, many viruses can outsmart that

system by blocking one of the steps further down the cascade.

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.

This work is 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

Director of Defense Research & Engineering (now the Assistant Secretary of

Defense for Research and Engineering).

--------------------------------------------------------------------------------

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff)

from materials provided by Massachusetts Institute of Technology. The original

article was written by Anne Trafton, MIT News Office.