Posted on 05/18/2003 7:28:00 PM PDT by Lessismore
The unprecedented computer and brain power focused on the severe acute respiratory syndrome (SARS) outbreak is beginning to yield hints about how to fight the disease. Within 3 weeks of fingering the culprit, scientists in several labs had sequenced the novel 30,000-base coronavirus. Last week, researchers from Singapore described their comparison of sequences drawn from 14 patients around the world, providing insights on the mutation rate of the virus and tools to track its spread. And on 13 May, researchers from Germany used the sequence to work out a probable structure for one of the key proteins involved in the virus's replication, a development that could provide a possible drug target.
The progress has been impressive. In the last month, labs have produced "more coronavirus sequences than I've seen in my 18-year career," says coronavirus expert Mark Denison of Vanderbilt University in Nashville, Tennessee. But the most effective tool against the disease is still the same one used to fight 19th century cholera outbreaks: quickly tracing and isolating the contacts of stricken patients before they spread the virus further.
Hoping to learn how fast the virus is changing, Edison Liu and his colleagues at the Genome Institute of Singapore compared isolates of SARS coronavirus from five patients in Singapore. They then compared these isolates to those sequenced by teams in Canada, the United States, and China. In a paper published online on 9 May by The Lancet, the team reported that overall, the virus is relatively stable compared to many other RNA viruses. Some scientists had hoped for signs that the virus was becoming less virulent, but Denison says such a systematic change could easily take years or even decades instead of weeks.
Of the 127 changes, the team found 16 examples that were present in more than one isolate--a sign that the mutation was present in the original virus cultured from the patient and was not a lab artifact. The distinctive variations may offer a tool with which to trace the spread of the virus. Sequences isolated from patients whose infections can be traced to a sick doctor at the Metropole Hotel in Hong Kong have a pattern distinct from those in Beijing and Guangdong.
In animal coronaviruses, scientists have documented several examples in which single nucleotide changes can dramatically alter the virus's behavior. But until the different symptoms and severity of SARS are better understood, it will be difficult to tell what--if anything--the genetic variations mean for the behavior of this virus, says Earl Brown of the University of Ottawa.
Meanwhile, different teams are using the new sequence data to search for the virus's potential weak spots. On 13 May, Science published a paper online (www.sciencemag.org/cgi/content/abstract/1085658) describing the crystal structures of a key protein from two coronaviruses: one that causes mild cold symptoms in humans and one that infects pigs. Rolf Hilgenfeld of the University of Lübeck, Germany, and colleagues then used the known structures and the sequence of the protein from the SARS virus to build a probable model of the new virus's protein. The protein is a crucial piece of the virus's replication cycle, notes Denison, and compounds that block it could make an effective treatment.
So far, old-fashioned tracking and isolation of patient contacts does seem to be paying off. On 28 April, Vietnam became the first country to be declared free of SARS. The outbreaks in Toronto and Singapore are also tapering off. In Hong Kong, progress is slower. On 12 May, officials reported just five new cases in the city, according to the World Health Organization (WHO), down from more than 100 a day at the epidemic's peak. But the city is not out of the woods: WHO officials said last week they could not identify the source of infection for nearly 9% of probable cases. They also agreed that the virus is more deadly than it originally appeared. When they factored in patients who are hospitalized for weeks before succumbing to SARS, the death rate climbed to nearly 15%. For patients over 65, the death rate is 50%.
A sensitive diagnostic test to quickly identify people infected with the SARS coronavirus is at the top of many public health officials' wish lists. Christian Drosten of the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, says the relative stability of the virus should help scientists develop just such a test. If all goes well, he says, it could be ready within a few weeks.
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