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Most
bacterial infections can be treated with antibiotics such as penicillin,
discovered decades ago. However, such drugs are useless against viral infections.
Now,
in a development that could transform how viral infections are treated, a team
of researchers at the Massachusetts Institute of Technology’s (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 in 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 Scott Wick, Christina
Zook, Tara Boettcher, Jennifer Pancoast, and Benjamin 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.
Todd Rider invented the PANACEA and DRACO antiviral therapeutics, and previously invented the CANARY (Cellular Analysis and Notification of Antigen Risks and Yields) sensor for rapid pathogen detection and identification. |
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.
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.
Filed Under: Drug Discovery
