Virology, Nebraska Center for

 

Authors

Navid Madani, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA
Arne Schön, Department of Biology, The Johns Hopkins University, Baltimore, MD
Amy M. Princiotto, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA
Judith M. LaLonde, Chemistry Department, Bryn Mawr College, Bryn Mawr, PA
Joel R. Cpurter, Department of Chemistry, University of Pennsylvania, Philadelphia, PA
Takahiro Soeta, Department of Chemistry, University of Pennsylvania, Philadelphia, PA
Danny Ng, Department of Chemistry, University of Pennsylvania, Philadelphia, PA
Liping Wang, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA
Evan T. Brower, Department of Biology, The Johns Hopkins University, Baltimore, MD
Shi-Hua Xiang, University of Nebraska-LincolnFollow
Young Do Kwon, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Chih-chin Huang, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Richard Wyatt, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Peter D. Kwong, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Ernesto Freire, Department of Biology, The Johns Hopkins University, Baltimore, MD
Amos B. Smith III, Department of Chemistry, University of Pennsylvania, Philadelphia, PA
Joseph Sodroski, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, MassachusettsFollow

Date of this Version

2008

Citation

Structure. 2008 November 12; 16(11): 1689–1701.

Comments

Copyright 2008 Madani et al.

Abstract

Human immunodeficiency virus (HIV-1) interaction with the primary receptor, CD4, induces conformational changes in the viral envelope glycoproteins that allow binding to the CCR5 second receptor and virus entry into the host cell. The small molecule NBD-556 mimics CD4 by binding the gp120 exterior envelope glycoprotein, moderately inhibiting virus entry into CD4-expressing target cells, and enhancing CCR5 binding and virus entry into CCR5-expressing cells lacking CD4. Studies of NBD-556 analogues and gp120 mutants suggest that: 1) NBD-556 binds within the Phe 43 cavity, a highly conserved, functionally important pocket formed as gp120 assumes the CD4- bound conformation; 2) the NBD-556 phenyl ring projects into the Phe 43 cavity; 3) enhancement of CD4-independent infection by NBD-556 requires the induction of conformational changes in gp120; and 4) increased affinity of NBD-556 analogues for gp120 improves antiviral potency during infection of CD4-expressing cells.

Share

COinS