This astonishing little trick
promises to make viral infections largely a thing of the past. If we can also do the same with plants while
we are at it, then one of the most persistent disease vectors will be largely eliminated.
Stopping viruses generally will
also eliminate a lot of hidden diseases we plausibly do not know even exist. Having a plant and animal culture that is
reliably viral disease free will be an economic boon to the globe.
This is an extraordinary bit of
work that we will hear a lot more about.
New drug could cure nearly any viral infection
by Anne Trafton for MIT News
The microscope images above show that DRACO successfully treats viral infections. In the left set of four photos, rhinovirus (the common cold virus) kills untreated human cells (lower left), whereas DRACO has no toxicity in uninfected cells (upper right) and cures an infected cell population (lower right). Similarly, in the right set of four photos, dengue hemorrhagic fever virus kills untreated monkey cells (lower left), whereas DRACO has no toxicity in uninfected cells (upper right) and cures an infected cell population (lower right).
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
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
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
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 and Engineering (now the Assistant Secretary of
Defense for Research and Engineering).
This research was published in a paper
July 27 in the journal PLoS One.
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