iruses and bacteria are often lumped together as germs. But
when it comes to drugs to treat the illnesses they cause, the
microbes are worlds apart.
There are dozens upon dozens of drugs that kill bacteria, the
first ones discovered in the 1920's. Although resistance by bacteria
to these antibiotics is a problem, the drugs often work quickly to
kill the bugs and cure the patient.
With viruses, the story is different. There are only about three
dozen antiviral drugs, and half were developed only in the last 15
years to treat a single disease, AIDS. Antiviral drugs usually do
not cure the disease, only slow the virus or reduce the symptoms.
Scientists have never been able to cure the most ubiquitous viral
disease, the common cold.
The dearth of antiviral drugs has been brought into focus by the
inability to treat SARS, the newly emerging viral infection that
kills perhaps as many as 20 percent of the people who contract
"We have no arsenal of antivirals for these emerging infections
that we are beginning to see," said Dr. John A. Secrist III,
president-elect of the International Society for Antiviral Research
and vice president for drug discovery at the Southern Research
Institute, a nonprofit organization in Birmingham, Ala.
Doctors have long wished for drugs that will act against viruses
the way antibiotics destroy bacteria. But in recent years their
worries have increased. Nowadays, when new viruses emerge, they can
spread quickly through modern transportation, as was the case with
SARS and West Nile virus, to name just two.
Also, health authorities must worry about bioterrorism with
viruses like smallpox, which has been eradicated as a natural
disease, and Ebola, which occurs only sporadically. "Bioterrorism
has reignited the need for countermeasures against viruses which in
their natural setting would not be a very big public health
problem," said Dr. Anthony S. Fauci, director of the National
Institute of Allergy and Infectious Diseases.
The traditional way of dealing with viruses, and in many cases
the most effective, has been through vaccines, which prevent
illness. But scientists say drugs are still needed to treat
infections after they occur because it is impractical to vaccinate
everyone against every conceivable virus.
For example, the government's effort to vaccinate health care
workers against smallpox has fallen well behind its goals, in part
because the vaccine itself can have harmful side effects. And for
some viruses, vaccines do not exist.
But if the need for antiviral drugs is growing, so are the tools
to make them. These have been largely honed in the war against AIDS.
Scientists have learned a lot about how viruses work and how to
design drugs to stop them. And the complete genetic sequence of a
virus can now be determined in days ?as was done for the SARS virus
?providing clues for mounting an antiviral attack.
"Almost any virus can be subject to chemical attack now, if it's
important enough to mount the effort," said Dr. Robert C. Gallo,
director of the Institute of Human Virology at the University of
Maryland and co-discoverer of H.I.V., the virus that causes AIDS.
"Prior to AIDS," he added, "most people didn't think it was doable."
Antivirals are a rapidly growing part of the pharmaceutical
industry, though still small, with most of the major companies
involved. Sales of such drugs last year totaled $5.6 billion in the
United States, up 20 percent from 2001, according to NDCHealth, a health care information
To get a toehold in the antiviral sector, Novartis, the Swiss drug giant, recently agreed to pay $255
million for a majority stake in Idenix Pharmaceuticals, a hepatitis
drug developer in Cambridge, Mass. Gilead Sciences of Foster City, Calif., which
has developed four antiviral drugs, including Viread for AIDS and
Tamiflu for influenza, now has the third-highest stock market
valuation in the biotechnology industry, behind Amgen and Genentech.
Still, most industry interest has been in H.I.V, hepatitis B and
C and influenza. It remains unclear whether they will deem it worth
the effort to develop drugs for other viruses. That includes SARS,
caused by a type of coronavirus, since experts still do not really
know whether it will become a major problem or just a sporadic one.
Dr. Norbert Bischofberger, executive vice president for research
and development at Gilead, said that he was "100 percent confident"
that his company could develop a drug for SARS but that he did not
expect to do so, because he thought that the disease would not be a
major one. "To do something against this coronavirus takes the same
amount of effort as any other target," he said. "At the end, you
would not have a product that you could sell."
There are several reasons the development of antiviral drugs has
lagged behind that of antibacterial drugs. Bacteria are
self-contained living creatures. They have a range of metabolic
functions and structures that can be disrupted to kill the organism.
Many of these functions or structures are different enough from
their human equivalents that they can be attacked without harming
the person taking the drug.
Viruses, by contrast, are little more than genetic material, either
DNA or RNA, and perhaps some enzymes, wrapped in a protein coat.
Technically speaking, they are not even alive.
"You can't kill something that is not living," said Dr. Nathaniel
A. Brown, a senior vice president at Idenix. "The only thing you can
inhibit for a virus is replication."
Moreover viruses make copies of themselves by hijacking the
machinery of the cells they infect. As a result, as Dr. Bischofberger
put it, "It's hard to kill the virus without killing the cell."
Some viruses can also remain dormant in the body without
replicating, thereby avoiding drugs that inhibit replication. The
chickenpox virus, for instance, can hibernate in nerve cells, emerging
years later in the form of shingles.
Viruses can replicate rapidly and, in many cases sloppily, giving
rise to mutations that make them resistant to drugs, though bacteria
can also evolve resistance. And for fast-moving viral infections like
flu or a cold, a drug must be very powerful to make a difference
before the disease runs its natural course.
"By the time you feel sick, the virus has replicated already and
spread to somebody else," said Dr. L. W. Enquist, a professor of
molecular biology at Princeton and the editor in chief of The Journal
Still, scientists and drug companies have developed several
techniques to slow down viruses. For H.I.V., four classes of drugs
have been developed.
The most common uses sort of a Trojan horse method. To replicate,
H.I.V. uses an enzyme called reverse transcriptase to turn its genetic
material, which is made of RNA, into DNA. So some AIDS drugs consists
of DNA building blocks that are slightly defective. The reverse
transcriptase is fooled into incorporating these mimics into the
replicating DNA chain. But once that happens, the chain can no longer
Another class of AIDS drugs work by binding to the reverse
transcriptase enzyme at a different place, inhibiting its function. A
third class of drugs blocks an enzyme called protease, also necessary
for viral replication. The newest class of drugs tries to prevent the
virus from getting into human cells in the first place. The first such
drug, Fuzeon, developed by
and Roche, was approved in March.
Drugs for other viruses employ similar tactics. There are several
drugs available to treat viruses belonging to the herpes family, which
cause ailments like cold sores, genital herpes, chickenpox, shingles
and encephalitis, a possibly fatal inflammation of the brain. Many of
these drugs, like acyclovir, inhibit an enzyme called polymerase,
which builds DNA much as reverse transcriptase does. The two drugs
approved for hepatitis B, lamivudine and adefovir, work similarly.
Other approaches are also being tried. One is to boost the body's
immune system to help fend off the virus. Alpha interferon, used to
treat hepatitis C, works partly this way. Another is to silence
specific genes needed by the virus using techniques known as antisense
or the newer RNA interference.
Both of these approaches provide possible ways to treat many
different viruses, with the gene silencing technique requiring only
changing the genetic sequence programmed to be silenced. Drugs that
inhibit viral enzymes generally work for only one type of virus,
although there are some exceptions.
One exception is cidofovir, approved to treat cytomegalovirus, a
member of the herpes family. It has also been shown to be effective
against pox viruses as well and is therefore a candidate to be used to
treat smallpox infections.
Government scientists are also screening existing antiviral drugs
as well as other drugs to see if any work against the SARS virus.
Rimantidine, an older flu drug, as well as beta interferon, an immune
system protein, have shown some effectiveness but in amounts that
would be too large to give to people, said Dr. Fauci.
Even if large companies sit back, many university scientists and
small companies are trying to develop or find drugs that can inhibit
the polymerase or protease enzymes used by the SARS virus. Dr. David
Ho, a well-known AIDS researcher in New York, and collaborators in
Hong Kong have already announced development of a compound that in the
test tube can block SARS from entering into human cells, much as
Fuzeon does for H.I.V.
Doctors say there is still need for better drugs for hepatitis B
and C and H.I.V. because existing drugs do not always work and can
have severe side effects. More drugs are also needed for other
viruses, including respiratory syncitial virus, which kills about
11,000 Americans a year, and human papillomavirus, which causes
As for the common cold, although there are many remedies for
symptoms like coughs or runny nose, no drugs directly attack the
Colds are caused by a variety of viruses, making it hard for a
single drug to work on all of them. Moreover since a drug would be
used by millions of people for a nonserious disease, a cold remedy
would have to be extremely safe for its benefits to outweigh its
risks. Safety concerns led to rejection last year of an antiviral drug
that could shorten a cold's length from seven days to six.
"Until we get a cure for the common cold, the field will always be
thought to have not achieved success," said Dr. Frederick G. Hayden, a
respiratory virus specialist at the University of Virginia. But
focusing on the common cold, he and others said, belies the strides
made in antiviral drug development and the far more serious challenges