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F glycoprotein from respiratory syncytial virus (RSV) is involved in membrane fusion events associated with the infection of host cells. Inhibition of RSV F glycoprotein (RSV F) with small molecules is a promising therapeutic strategy against the virus, but the mechanism involved has been unclear. A structural approach now shows binding of such small-molecule inhibitors in a three-fold-symmetric pocket within the central cavity in the prefusion conformation. This stabilizes that conformation and blocks the conformational changes required for fusion with host membranes. Cover image created by Michael B. Battles. Cover design by Erin Dewalt. Article, p87(In the version of the cover caption initially published, the cover artwork was credited to Erin Dewalt, based on imagery from the author, rather than stating that it was created by Michael B. Battles and the design was by Erin Dewalt. The error has been corrected in the HTML and PDF versions of the caption as of 11 February 2016.)
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The binding of small-molecule inhibitors of the RSV F glycoprotein in a central cavity in the prefusion conformation stabilizes this conformation and blocks the conformational changes required for fusion with host membranes.
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