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Learning how SARS spikes its quarry

Researchers have determined the first detailed molecular images of a piece of the spike-shaped protein that the SARS virus uses to grab host cells and initiate the first stages of infection. The structure, which shows how the spike protein grasps its receptor, may help scientists learn new details about how the virus infects cells. The information could also be helpful in identifying potential weak points that can be exploited by novel antiviral drugs or vaccines.

The SARS (severe acute respiratory syndrome) coronavirus was responsible for a worldwide outbreak in 2002-2003 that affected more than 8,000 people and killed 774 before being brought under control. Public health experts worry about another outbreak of the virus, which originates in animals such as civet cats.

The research team, led by Howard Hughes Medical Institute investigator Stephen C. Harrison at Children's Hospital and Harvard Medical School, and colleague Michael Farzan, also at Harvard Medical School, reported its findings in the September 16, 2005, issue of the journal Science. Lead author Fang Li in Harrison's laboratory and Wenhui Li in Farzan's laboratory, also collaborated on the study.

According to Harrison, prior to these studies, researchers knew that one of the key steps in SARS infection occurs when the virus's spike protein attaches to a receptor on the surface of target cells. Attachment of the spike protein permits the virus to fuse with a host cell and inject its RNA to infect the cell.

A detailed understanding of how the spike protein complexes with its receptor, ACE2 (angiotensin-converting enzyme 2), could have important clinical implications. "The interest in understanding this complex has to do with the fact that this virus jumps from animals to humans, laterally among humans, and in some cases from animals to humans but without subsequent human-to-human transmission," said Harrison. "And we know that those modes of transmission depend on specific
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
15-Sep-2005


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