[中文翻譯之前有貼過類似的，想看原文的這個寫的蠻容易懂得]
SARS' Achilles' heel revealed
--Drugs to treat common cold may be effective against the virus.
15 May 2003
Researchers have made a three-dimensional image of a crucial part of
the virus that causes severe acute respiratory syndrome (SARS). The model
suggests that a drug being tested as a cold remedy is a good starting
point in treating the killer disease.
Another group has already tested the molecule, called AG7088, against
the SARS virus in the test tube. Results have been negative, says virologist
Robert Baker of the US Army Medical Research Institute of Infectious Diseases
(USAMRIID) in Fort Detrick, Maryland. "Yet that result is preliminary and we
are re-testing now," he says.
But many very similar chemicals show activity against SARS, suggesting
that researchers are closing in on the right target, says Baker.
The drug blocks a component of the virus called a proteinase. All
coronaviruses, the family to which the SARS virus belongs, rely on these
molecules to reproduce.
"It's the Achilles' heel of the virus," says biochemist Rolf Hilgenfeld
of the University of Lubeck in Germany, who led the team behind the model.
"We're convinced that hitting this target will be enough to stop infection."
To sculpt their SARS target, Hilgenfeld's team used models of two
coronavirus proteinases that they were studying before the outbreak. One
virus causes diarrhoea in pigs, the other triggers cold-like symptoms in
humans. The team's computer model is based on these proteinase structures and
the SARS genome1.
In the groove
AG7088 fits a cleft in the proteinase, the analysis revealed. Like a
chemical spanner in the virus' works, the molecule should prevent the
proteinase from working.
"It doesn't fit very well," admits Hilgenfeld. "But it will be a very
good starting point."
AG7088 is in human tests now - the drug company Pfizer created it to
block the proteinase of an unrelated cold virus. The chemical has so far
proved to be safe, and a modified version would probably take less time to develop into a SARS drug.
The drug is one of about 100 candidate compounds loaned by drugs
companies to the USAMRIID. If, as is likely, none is a perfect match, the
German team's structure, combined with the molecules, "should quickly lead
to a wealth of good leads we can follow up", says Baker.
If a ready-made drug to treat SARS cannot be found, Hilgenfeld and his
colleagues advocate using their model to design a better SARS blocker. This
strategy was used to design the latest HIV drugs.
The other, and some would argue quicker, approach is to screen chemicals.
In the past month, USAMRIID scientists have tested around 120,000 compounds
for activity against SARS. Given the urgency of finding a treatment, both
approaches should continue. The rational approach, says Baker, "will find
leads that we wouldn't necessarily run across using brute force".
References
Anand, K., Ziebuhr, J., Wadhwani, P., Mesters, J. R. & Hilgenfeld, R.
Coronavirus Main Proteinase (3CLpro) Structure: Basis for design of anti-SARS
drugs. Science, Published online, doi:10.1126/science.1085658 (2003).
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