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Scientists taking close look at SARS virus

By STEVE MITCHELL, UPI Medical Correspondent   |   May 21, 2003 at 8:00 PM   |   Comments

WASHINGTON, May 21 (UPI) -- Scientists racing to understand the virus that causes severe acute respiratory syndrome said Wednesday they are making important discoveries about its actions at the molecular level.

The discoveries could aid the search for effective medications against the deadly pathogen, researchers told United Press International.

The SARS virus, which has infected nearly 8,000 people around the world and caused the death of more than 660, is a novel organism that has never been seen before in humans or animals.

Although it is similar to other microbes that come from a group known as coronaviruses, scientists who decoded the genome of the SARS virus found it contains genes that make it unique.

Previously known coronaviruses generally cause mild respiratory illnesses in humans, so experts were shocked to find SARS could be so deadly. Now they are trying to understand how the virus functions and causes the illness.

"Nobody expected such a severe pathogen to come from the coronavirus family ... so (the SARS outbreak) was like Sept. 11 for corona virologists," said Mikhail Rozanov, a coronavirus expert who will present information about the SARS virus at a scientific meeting next week in the Netherlands.

"We don't know the mechanism yet the virus uses to kill cells ... but it may be a combination of directly killing cells" and an over-response of the immune system attacking and killing infected cells, said Dr. Mark Denison, a renowned coronavirus expert at Vanderbilt University School of Medicine in Nashville.

The virus appears to function similar to other coronaviruses, so one explanation for its lethality simply could be because it is entirely new. Therefore, humans have not yet built up an immunity to it, Denison said. That could explain why it can cause respiratory problems and even death in some people.

Although coronaviruses typically cause mild illness in people, some coronaviruses that infect animals "are quite deadly," so it would not be unusual for this new virus to be fatal in people, he said.

Additional studies currently being conducted around the globe will be necessary to understand how the virus exerts its virulence, Denison said. "Corona virologists don't feel ... that the virus is organized differently or has characteristics that we could say just by looking at it make it a killer virus," he noted.

One finding so far is that the SARS virus rapidly kills cells in test tubes, Denison said.

"In culture, it kills cells pretty readily," he said. "Within 24-48 hours, it causes (cells) to die."

That is not unusual, however, because other viruses can be just as deadly, he explained.

The virus also causes cells of the body to fuse together. Other viruses do that, too, and this could explain one mechanism of how the virus makes people sick, Denison said.

Another possibility is eight proteins express by the virus' genome that have never been seen before. Some of these could play a role in the ability of the virus to infect cells and cause disease, Rozanov said.

"By itself, the presence of an unknown protein is not something that would make you say, 'Oh, I found the pathogenic identity of the virus,'" he said. "However, none of the other coronaviruses have these proteins ... so this may be a target of research to" understand how the virus causes disease.

"Any of these (eight proteins) might be involved in pathogenesis ... and unusual symptom development for coronaviruses," he said, adding the research still is in its early phases and scientists still do not know which if any of these eight proteins are expressed or utilized by the virus.

"We are pretty far away from understanding what those proteins might do and where they could act in the cell," Rozanov said. But he noted preliminary evidence "strongly supports the idea that the SARS coronavirus indeed expresses those unusual proteins, at least some of them."

Some of the proteins look like they "may bind to cell membranes or be inserted into cell membranes" to help the virus infect cells, he said. But that remains to be determined by additional studies.

Rozanov said understanding fully how the virus causes illness could take months or years. "It's hard to tell in advance how soon it might be. A matter of a few months at least," he said.

Learning exactly how the virus causes disease could be useful for designing medications that are effective against the virus and Rozanov is working as a contractor for the National Center for Biotechnology Information, a component of the National Institutes of Health, on a project using computer analysis to analyze the SARS virus in a search for therapies. Rozanov's comments do not represent the NIH's view.

Rozanov is using computers to compare proteins from the SARS virus to proteins of other pathogens. The goal is to identify the viral proteins similar to proteins from other germs that already are vulnerable to drugs to clue researchers in designing effective new medications.

This approach could yield candidate drugs sooner than experiments done with the actual SARS virus, he said.

Scientists also are obtaining clues about effective medications from ongoing research at the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md. Researchers there are testing drugs and other compounds on the SARS virus to determine if any might be effective against it.

"We're beginning to get an idea of what an active molecule might look like," said John Huggins, chief of the viral therapeutics branch in the virology division at USAMRIID. "We have been able to find some compounds that show activity and we're working with (other researchers) to determine whether those or related compounds may be potential candidates."

By finding a drug or compound that works against the virus, researchers get an idea of what an effective drug should look like at the molecular level, he said. Then they can look around for closely related compounds and test those to see if any are effective, he said.

Last week, researchers said their analysis of the virus suggested a drug already being tested in humans to treat the common cold could, with some modification, be effective against SARS. The drug, which is aimed at different kind of virus, is targeted against a protein that is very similar to one produced by the SARS virus and that is essential to the virus' ability to replicate.

Other research going on at the NIH involves developing an animal model of SARS that mimics the symptoms of the disease seen in humans. Researchers there are attempting to inoculate monkeys with the SARS virus, said Anthony Fauci, director of National Institute of Allergy and Infectious Diseases. This would be a valuable model because monkeys are very close to humans genetically and this would give researchers a good surrogate for testing vaccines as well as potential new medications, Fauci said.

Denison said the race to get out new findings about the virus will slow now as the SARS outbreaks around the world begin to dwindle. This will allow for "more detailed analysis" of the virus, which could aid in a better understanding of it.

However, developing a treatment for SARS may still be urgent as U.S. health officials testified before the Senate Wednesday they expect the disease to return this winter.

© 2003 United Press International, Inc. All Rights Reserved. Any reproduction, republication, redistribution and/or modification of any UPI content is expressly prohibited without UPI's prior written consent.
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