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Journal of Virology, July 2003, p. 7669-7672, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7669-7672.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Direct Evidence that C-Peptide Inhibitors of Human Immunodeficiency Virus Type 1 Entry Bind to the gp41 N-Helical Domain in Receptor-Activated Viral Envelope

Panacos Pharmaceuticals Inc., Gaithersburg, Maryland 20877

Received 30 October 2002/ Accepted 28 March 2003

While it has been established that peptides modeling the C-helical region of human immunodeficiency virus type 1 gp41 are potent in vivo inhibitors of virus replication, their mechanism of action has yet to be determined. It has been proposed, but never directly demonstrated, that these peptides block virus entry by interacting with gp41 to disrupt the formation or function of a six-helix bundle structure. Using a six-helix bundle-specific monoclonal antibody with isolate-restricted Env reactivity, we provide the first direct evidence that, in receptor-activated viral Env, C-peptide entry inhibitors bind to the gp41 N-helical coiled-coil to form a peptide/protein hybrid structure and, in doing so, disrupt native six-helix bundle formation.

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