Here's some news that suggests the SARS protease is similar to that of the rhinovirus. Don't know of anyone else working on the rhinovirus protease (didn't even know that PFE was working on this). A fair number of biotechs (aside from big pharma) have expertise in other protease inhibitors - e.g., VRTX (HIV, HCV protease), VPHM (HCV protease). (VPHM's would-be cold-drug, pleconaril, was not a protease inhibitor).
Cold drug could yield SARS treatment
By Steve Mitchell
UPI Medical Correspondent
From the Science & Technology Desk
Published 5/13/2003 1:51 PM
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WASHINGTON, May 13 (UPI) -- A drug currently being tested in humans to prevent the common cold could lead to treatments for severe acute respiratory syndrome, a study released Tuesday suggests.
So far, scientists have not yet identified an effective medication against the SARS virus, which has spread quickly around the world infecting more than 7,000 people and causing more than 500 deaths. But the new study gives hope an effective treatment could be developed.
Researchers conducted molecular analysis of the SARS virus and found a drug called AG7708, which is being developed to treat the common cold, "might be a good starting point for the development of drugs against" the organism, the study's principal investigator, Rolf Hilgenfeld of the University of Luebeck, Germany, said during a teleconference from Germany.
In the study, which is being released on the Web site of the journal Science, Hilgenfeld's group found a protein expressed by the SARS virus is very similar to a protein expressed by the rhinovirus, which causes the common cold. Because the protein is an enzyme called protease, which is essential to the replication cycle of the virus, blocking the protease should keep the virus from making copies of itself and thereby prevent the breathing problems and death seen in some SARS patients.
AG7708 is under development by Pfizer Inc., the pharmaceutical manufacturer, as a cold treatment and it already has reached advanced stages of clinical testing. Pfizer representatives did not respond to inquiries from United Press International.
Dr. Mark Denison, an associate professor of infectious diseases at Vanderbilt University Medical Center in Nashville, told UPI, the protease "is probably the most import target in viral replication right now that can be attacked."
Denison noted the ongoing program at the U.S. Army Medical Research Institute of Infectious Diseases in Ft. Detrick, Md., to search for drugs that could be potential SARS treatments already is testing compounds that inhibit proteases -- because many researchers had theorized it was an obvious target on which to base treatments.
Gilbert Chin, an editor at Science, said during the teleconference the journal had received the study about a month ago. The journal held onto it before releasing it to researchers and the public so the study could be subjected to "a very rigorous peer review" to ensure the results were valid and accurate, he explained.
Hilgenfeld's team used data from two viruses similar to the SARS virus to construct a three-dimensional model of the SARS protease.
The researchers found the SARS protease is similar in structure and activity to the rhinovirus protease. They had designed an inhibitor for this protease for another virus that infects pigs and they found it resembled the AG7708 drug.
"The drug doesn't fit perfectly ... but it's a very good starting point for designing drugs that fit better," Hilgenfeld said. The researchers did not test AG7708 directly against the SARS virus, but instead used their structural analysis of how the drug interacts with the rhinovirus protease to conclude it might be a close-fit with the SARS protease.
Denison said the findings are important because they help elucidate the chemical structure of the SARS protease and give researchers a basis for making "chemical alterations to (currently available protease inhibitors) to increase their activity" against the SARS virus, he said.
However, it probably will take some time to develop a SARS treatment because any newly designed compounds still would have to be tested to determine if they are effective, he said. "It doesn't solve the problem but it gives another approach to pursuing particular treatments," he said.
Hilgenfeld agreed, saying it "will still be probably a couple of years until an approved drug is available to treat SARS on this basis."
It "will be a matter of a few months before one could come up with an improved compound" to inhibit the SARS virus, he said. And that compound will then have to go through toxicity testing and clinical trials before it is approved for use in humans to treat SARS, he added.
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