Keynote review: Progress in targeting HIV-1 entry

The finding that inhibiting the reduction of gp120 disulfide bonds prevents HIV-1 entry into human cells opens new opportunities for drug development Current HIV entry inhibitors target the binding of the viral envelope glycoprotein gp120 to cellular CD4 and co-receptors, or block a late stage of th...

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Bibliographic Details
Published inDrug discovery today Vol. 10; no. 16; pp. 1085 - 1094
Main Authors Ryser, Hugues J.-P., Flückiger, Rudolf
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 15.08.2005
Subjects
CD4
conformational changes
disulfide bonds
entry inhibitors
gp120
gp41 activation
HIV-1 entry
PDI
Protein disulfide isomerase
virus-cell fusion
Protein disulfide isomerase
Pharmaceutical Science
Structural Biology
Drug Discovery
HIV-1 entry
Virology
disulfide bonds
CD4
PDI
entry inhibitors
Chemical Biology
gp120
conformational changes
gp41 activation
virus-cell fusion
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Summary:The finding that inhibiting the reduction of gp120 disulfide bonds prevents HIV-1 entry into human cells opens new opportunities for drug development Current HIV entry inhibitors target the binding of the viral envelope glycoprotein gp120 to cellular CD4 and co-receptors, or block a late stage of the fusogenic activation of adjacent gp41. New targets are suggested by the role of cell surface protein disulfide isomerase (PDI), which attaches to the primary receptor CD4 close to the gp120-binding site. This could enable PDI to reduce gp120 disulfide bonds, which triggers the major conformational changes in gp120 and gp41 required for virus entry. Inhibiting cell surface PDI prevents HIV-1 entry. The new potential targets outlined are PDI activity as well as the sites of PDI-CD4 and PDI-gp120 interaction.
ISSN:1359-6446
1878-5832
DOI:10.1016/S1359-6446(05)03550-6