Posted on 11/30/2003 3:11:48 PM PST by CathyRyan
A year ago, a mystery virus began to kill people in China. Causing an illness dubbed severe acute respiratory syndrome (SARS), the virus quickly spread beyond Asia and for a few months stirred fears of a worldwide epidemic.
With stunning speed, scientists identified the virus and decoded its genetic sequence (SN: 4/26/03, p. 262:
http://www.sciencenews.org/20030426/fob8.asp).
Now, a research team has claimed victory in the race to identify the cellular receptor—the protein to which the virus attaches when it infects cells—for the SARS virus. Since the protein turned out to be a well-known one that had previously been implicated in heart disease, drugs that target the receptor are already under development. Some of those same compounds might serve as antiviral medications for SARS patients, say researchers.
Michael Farzan of Brigham and Women's Hospital in Boston and his colleagues went fishing for the receptor with a lure made of the molecule on the surface of the SARS virus that docks with the cell's receptor. They burst monkey-kidney cells, which the virus easily infects, and then cast the viral-surface molecule into the resulting debris.
The SARS-receptor molecule latched on to three proteins, but only one of these, angiotensin-converting enzyme 2 (ACE2), is typically found on the surface of mammalian cells.
Several subsequent experiments, reported in the Nov. 27 Nature, make the case that the human form of ACE2 is a SARS-virus receptor. First, human-kidney cells engineered to produce ACE2 fuse with cells engineered to make the SARS virus' surface molecule. Second, cells engineered to mass-produce ACE2 were more readily infected by the SARS virus than were normal cells. Third, an antibody to ACE2 slowed the replication of the virus in cells bearing the enzyme.
"We nailed it. It's lock-solid" that ACE2 is a receptor for the SARS virus, says Farzan.
Another virologist trying to identify the receptor agrees. The results are "very convincing," says Dimiter S. Dimtrov of the National Cancer Institute in Frederick, Md. "It's absolutely amazing how quickly they did this."
Until now, ACE2 has largely interested cardiologists. Several decades ago, physicians began using inhibitors of a similar enzyme, ACE, to treat high blood pressure and heart disease. A few years ago, scientists discovered ACE2 and began to look for compounds that block its activities. There's a good correspondence between tissues that make ACE2—the heart, lungs, and kidneys, for example—and ones affected by the SARS virus, notes Farzan.
He and his colleagues are now looking into whether known ACE2 inhibitors block the SARS virus from cells. It's possible that these inhibitors may thwart ACE2's function but still allow the virus to grab onto the enzyme, cautions Farzan.
Gary Nabel, director of the National Institutes of Health Vaccine Research Center in Bethesda, Md., calls the new work a "fascinating discovery" but notes that the SARS virus may exploit proteins other than ACE2 as receptors.
Date: Fri 28 Nov 2003
From: ProMED-mail
Source: The Lancet, vol. 362, no. 9398, Fri 29 Nov 2003 [edited]
Hong Kong: Genotype of the SARS coronavirus from the Amoy Gardens outbreak
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[The following is the summary of a Research Letter in the current issue of the Lancet, in which the authors conclude that the different features of the hospital-based outbreak and the Amoy Gardens outbreak are the result of extraneous factors rather than differences in virus genotype. - Mod.CP]
Severe acute respiratory syndrome (SARS) is a global health concern. In Hong Kong, 2 major outbreaks, one hospital-based and the other in the Amoy Gardens apartments, were identified. The frequency of diarrhoea, admission to intensive care, and mortality differed significantly between the 2 outbreaks. We carried out genomic sequencing for viral isolates from 5 Amoy Gardens patients. The virus sequence was identical in 4 of these 5 patients. The sequence data from one hospital case and the 4 identical community cases had only 3 nucleotide differences. Alterations in the SARS coronavirus genome are unlikely to have caused the distinctive clinical features of the Amoy Gardens patients, and these results highlight the importance of non-viral genomic factors in this outbreak.
(By S S C Chim, S K W Tsui, K C A Chan, T C C Au, E C W Hung, Y K Tong, R W K Chiu, E K O Ng, P K S Chan, C M Chu, J J Y Sung, J S Tam, K P Fung, M M Y Waye, C Y Lee, K Y Yuen, Y M D Lo, and members of the CUHK Molecular SARS Research Group. From the Departments of Chemical Pathology (S S C Chim PhD, K C A Chan MRCP, Y K Tong MPhil, R W K Chiu MB, E K O Ng PhD, Prof Y M D Lo DM), Biochemistry (S K W Tsui PhD, T C C Au MPhil, K P Fung PhD, M M Y Waye PhD, Prof C Y Lee PhD), Paediatrics (E C W Hung MB), Microbiology (P K S Chan MRCPath, J S Tam PhD), and Medicine and Therapeutics (Prof J J Y Sung MD), Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China; Department of Medicine, United Christian Hospital, Hong Kong (C M Chu FRCP); and Department of Microbiology, Queen Mary Hospital, University of Hong Kong, Hong Kong (Prof K Y Yuen MD)
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