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Learning how SARS spikes its quarry

Thus, the structure reveals details about how even small mutations in the spike protein gene that alter the identity of amino acids at those sites can affect the virus's ability to infect humans. Such mutations enable viral transmission by altering the shape of the spike protein, which affects how well it binds to the ACE2 receptor, explained Harrison. In particular, he said, the new structure shows how mutation at one of the two sites can enable the animal SARS virus to infect humans, but by itself this mutation does not appear to allow subsequent human-to-human transmission.

"The observation is that a dramatic epidemiological difference can result from what looks like an almost trivial mutation," said Harrison. "These findings give us the beginnings of information needed -- if a new virus were isolated -- to make predictive guesses about infectivity, so that we can better give advance warning."

He also noted that laboratory studies indicate that the fragment of the spike protein they used could provide the basis of a vaccine against SARS, since it appears to be recognized by the immune system of the host.

In future studies, Harrison and his colleagues plan to explore the steps that occur after the spike protein attaches to the receptor. The researchers know that the spike protein undergoes a conformational change that enables the virus to fuse with the host cell.

"When there's a conformational change, it gives you an opportunity to explore the possibility of antiviral therapeutics," said Harrison. "When you have two conformational structures, you can think about how to prevent infection by inhibiting the transition from one state to another."


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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
15-Sep-2005


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