Virology, Nebraska Center for
Document Type
Article
Date of this Version
2008
Citation
Structure. 2008 November 12; 16(11): 1689–1701.
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.
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Cell and Developmental Biology Commons, Genetics and Genomics Commons, Infectious Disease Commons, Medical Immunology Commons, Medical Pathology Commons, Virology Commons
Comments
Copyright 2008 Madani et al.