Flu fears spur research into virus killers
Top scientists at federal health institutes, universities, and drug companies report that they are witnessing a surge of interest in finding treatments for viral infections -- fueled in part by fears of a global flu epidemic.
Once, viral disease researchers rarely heard from drug development companies. Now, scientists say, they regularly get calls from companies hoping to forge partnerships in the quest to discover antiviral medicines.
Scientists say they could be at the dawn of an unprecedented period of discovery in the hunt for drugs against viruses that cause hepatitis, respiratory ailments, and more exotic diseases.
The federal government's top disease specialist, Dr. Anthony S. Fauci, said the threat of a bird flu virus that could kill millions of people has compelled scientists to reconsider their research priorities.
''This kind of attention is causing us to shake the cages," Fauci, director of the National Institute of Allergy and Infectious Diseases, said in an interview at a flu preparedness summit in Boston last month. ''We've accepted less-than-optimal viral treatments. We've got to do better than that."
The campaign against bioterrorism also has boosted research on viruses, leading the government to more than double spending on the war against deadly germs of all kinds in the past five years.
For decades, medicines to fight viral infections have been a neglected aspect of drug research.
While viruses and bacteria both cause enormous human suffering, it's always been a lot easier to find bacteria-slaying antibiotics like penicillin, because they occur naturally wherever bacteria live, such as in the soil.
There's no such luck when it comes to antivirals. They have to be made in the lab, and scientists have to be careful not to cause collateral damage: Viruses invade human cells, so drugs to combat those germs must work like smart bombs to avoid damaging cells.
But the fears that bird flu could develop the ability to spread rapidly among humans, advances in research technology, and the growing realization that there's money to be made in antivirals is starting to change the landscape.
''There's been momentum building for antivirals for several years, perhaps picking up more recently with greater intensity," said Dr. Raphael Dolin, dean for Academic and Clinical Programs at Harvard Medical School. ''The paradox has been that viral infections are so prevalent and so important, and yet the number of antiviral drugs that have been developed are relatively few compared to the antibiotics."
There's no disputing the need: There are more drugs aimed at HIV -- about two dozen -- than there are for all other viral ailments combined.
There are the viral bugs that cause millions of colds and those responsible for the flu, which each year kills an estimated 36,000 people annually in the United States, mainly the very old and the very young. And there are viruses that while far less common are much more lethal: In every African outbreak of Ebola during the past three decades, more than half of those infected have died.
Companies increasingly appear to recognize that what makes good medical sense can also make good business sense.
The Swiss drug giant Roche Pharmaceuticals saw revenue from its flu pill Tamiflu soar more than fivefold in a single year, rocketing from $229 million in global sales in 2004 to $1.2 billion a year later.
And a report from the global consulting company Frost & Sullivan released last week forecast that the US market for drugs against hepatitis B and C will increase from about $2.2 billion last year to nearly $4.8 billion in 2012.
At least once a week, drug companies with a new virus-fighting strategy approach scientists at the US Centers for Disease Control and Prevention and ask for help -- a level of interest not evident until the past year, said Rick A. Bright, who until last month directed the antiviral drug program in the CDC's Influenza Branch.
Bright said he believes that lessons gleaned by drug researchers in the pursuit of new influenza medications can be translated to other viral conditions.
''Once they start learning the basics of antiviral drug development, they gain that experience, and they become much more interested in developing other antivirals," said Bright, who left the CDC to join a biotechnology company focused on vaccines.
Still, finding new drugs to treat viruses will never be as simple as scooping up a cup of dirt.
The British researcher Alexander Fleming stumbled upon the world's first antibiotic, penicillin, when he noticed that mold sprouting in a laboratory experiment had strangled the advance of bacteria. That was in 1928.
It would take another three decades before scientists introduced the first antiviral, a drug used to treat herpes infections in the eye. The antivirals that followed were the product of painstaking laboratory discoveries.
''I can't think of any antivirals that are licensed for use that were originally developed from natural products," said John Coffin, who specializes in studying the AIDS virus at Tufts University. ''But with antibacterials, it was a fairly simple matter to go into the soil or the sewer and start pulling out things and testing them in a very simple way to determine if they inhibited bacteria."
Bacteria possess an array of mechanisms that can be targeted by drugs. And because bacteria aren't dependent on humans -- or any other host -- for their survival and replication, drugs can kill bacteria without killing human cells. Studying bacteria in the laboratory is also a fairly straightforward process, with scientists able to grow the germs on a plate.
Doing battle with viruses is more complex -- in large part because of their simplicity. Viruses can range from one-fifth to one-100th the size of bacteria. And they are the ultimate parasite: They survive only if they hijack the cells of their victims; once inside, they begin churning out replicas of themselves.
Only with the introduction of increasingly sophisticated laboratory methods in the 1970s and 1980s were scientists able to efficiently study viruses. One pivotal technique involves creating a blueprint of a virus's three-dimensional architecture, showing the location of the separate atoms that constitute the virus.
But even when researchers acquired that ability, they had to approach the development of drugs to combat viruses with care.
''You have to design a drug where you don't just throw on gasoline," said Terrence M. Tumpey, a research scientist in the CDC's flu branch. ''Gasoline will kill the virus, but it will also do a number on your own cells."
Finding the right formula for a drug to defeat a virus is a daunting proposition -- a lesson learned during nearly two decades of research by
It was 1987 when scientists at BioCryst and the University of Alabama at Birmingham began unraveling the molecular fingerprint of a pivotal enzyme in the flu virus called neuraminidase. If they could figure out a way to block that enzyme, they could halt the march of the flu virus, said Dr. Claude Bennett, the company's president.
In 1998, BioCryst partnered with subsidiaries of a major drug company,
The deal with the big drug company ended even before tests of a pill version of the drug yielded disappointing results. The BioCryst scientists speculated that the pill failed to deliver enough medication to patients. Now the company is studying whether injections might be a more effective way to get the drug to patients, with studies in animals underway.
Some infectious disease specialists, such as Dr. Frederick G. Hayden of the University of Virginia, say that so far, it's mainly small research companies that have displayed the greatest enthusiasm for antivirals. Big drug companies, Hayden and other scientists say, remain mainly interested in developing blockbuster drugs against chronic conditions.
Still, some major pharmaceutical companies have made a commitment to developing medications for viral infections. Roche, for example, has scientists studying HIV, hepatitis B, hepatitis C, and the human papillomavirus, a sexually transmitted disease.
A top Roche scientist said the emergence of avian influenza -- and concerns that it will spark a human epidemic -- has reminded researchers that the war with viruses is far from won.
''Every time we think we have these viruses nailed down, then something else comes from another direction," said Nick Cammack, head of viral disease research at Roche's labs in Palo Alto, Calif. ''People are seeing a new disease is always coming along or an old one is just changing."
Stephen Smith can be reached at stsmith@globe.com. 
© Copyright 2006 Globe Newspaper Company.
