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dc.contributor.authorFrey, Gary
dc.contributor.authorRits-Volloch, Sophia
dc.contributor.authorZhang, X.-Q.
dc.contributor.authorSchooley, Robert
dc.contributor.authorChen, Bing
dc.contributor.authorHarrison, Stephen
dc.date.accessioned2019-10-13T16:03:26Z
dc.date.issued2006
dc.identifier.citationFrey, G., S. Rits-Volloch, X.-Q. Zhang, R. T. Schooley, B. Chen, and S. C. Harrison. 2006. “Small Molecules That Bind the Inner Core of Gp41 and Inhibit HIV Envelope-Mediated Fusion.” Proceedings of the National Academy of Sciences 103 (38): 13938–43. doi:10.1073/pnas.0601036103.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41542805*
dc.description.abstractHIV-1 enters cells by membrane fusion, mediated by the trimeric viral envelope glycoprotein gp160, which is processed by a single proteolytic cleavage into stably associated gp120 and gp41. The gp120/gp41 trimer can be triggered to undergo an irreversible conformational change. Using a protein-based assay designed to mimic the gp41 conformational change, we screened for small molecules that prevent the formation of postfusion gp41. Several compounds were identified. One set of structurally related molecules inhibited formation of a postfusion-like assembly with an IC50 of approximate to 5 mu M. The compounds also inhibited envelope-mediated membrane fusion in both cell-cell fusion and viral infectivity assays. Thus, our screen identifies effective fusion inhibitors. Tested against a panel of envelope proteins from primary HIV-1 isolates, the compounds inhibited fusion across a broad range of clades, including both M and T tropic strains. They bind in a highly conserved, hydrophobic pocket on the inner core of the gp41 trimer, a region previously identified as a potential inhibitor site.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleSmall molecules that bind the inner core of gp41 and inhibit HIV envelope-mediated fusion
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorHarrison, Stephen::29356e859c6d3698df98e8184352069e::600
dc.date.available2019-10-13T16:03:26Z
dash.workflow.comments1Science Serial ID 91963
dc.identifier.doi10.1073/pnas.0601036103
dash.source.volume103;38
dash.source.page13938


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