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BioAssay: AID 1991

Summary assay for the identification of Human Immunodeficiency Virus Fusion Inhibitors.

The fusion-active conformation of the envelope protein gp41 of HIV-1 consists of an N-terminal trimeric alpha-helical coiled coil domain, and three anti-parallel C-terminal helices which fold down the grooves of the coiled coil to form a six-helix bundle. Disruption of the six-helix bundle is considered to be a key component of an effective non-peptide fusion inhibitor. This structure forms as a more ..
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AID: 1991
Data Source: Burnham Center for Chemical Genomics (BCCG-A234-GP41-Inhibitors-Summary)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2009-10-19
Modify Date: 2011-04-20
Target
Depositor Specified Assays
Show more
AIDNameTypeComment
1986uHTS fluorescence assay for the identification of Human Immunodeficiency Virus Fusion Inhibitors.confirmatoryuHTS fluorescence assay for the identification of Human Immunodeficiency Virus Fusion Inhibitors.
2279A Cell Based Assay for the Identification of Lead Compounds with Inhibitory Activity against HIV-1 Fusion (CCR5 Tropic HIV-1 Fusion Inhibition Assay) - Dose ResponseconfirmatoryConfirmatory assay
2286A Cell Based Assay for the Identification of Lead Compounds with Inhibitory Activity against HIV-1 Fusion (CCR5 Tropic HIV-1 Fusion Inhibition Assay) - Cytotoxicity Counter Screen - Dose ResponseconfirmatoryConfirmatory assay
2644A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary AssayconfirmatorySecondary Assay
2649A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity ScreenconfirmatoryCytotox Assay
2788A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Assay (2)confirmatory
2812A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen (2)confirmatory
434967SAR analysis of compounds that inhibit Human Immunodeficiency Virus Fusion.confirmatory
435029SAR analysis of compounds that inhibit Human Immunodeficiency Virus Fusion, cell-cell fusion assayconfirmatory
435031SAR analysis of compounds that inhibit Human Immunodeficiency Virus Fusion, cytoxicity assayconfirmatory
493095SAR analysis of compounds that inhibit Human Immunodeficiency Virus Fusion -Set 2confirmatory
504341A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 Fusion Inhibition Assay) - Dose Response (1)confirmatory
504352A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Assay (3)confirmatory
504363A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 MAGI Antiviral Assay) - Dose Responseconfirmatory
504367A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 Fusion Inhibition Assay) - Dose Responseconfirmatory
504388A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 Fusion Inhibition Assay) - Secondary Cytotoxicity Screenconfirmatory
504393A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screenconfirmatory
504394A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 Fusion Inhibition Assay) - Secondary Cytotoxicity Screenconfirmatory
504395A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen (3)confirmatory
504484A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CXCR4-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Responseconfirmatory
504503A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CCR5-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Responseconfirmatory
504530A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (HIV-1 PBMC Assay) - Cytotoxicity Counter Screen - Dose Responseconfirmatory
504551A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 Fusion Inhibition Assay) - Dose Response (2)confirmatory
504553A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Assay (4)confirmatory
504560A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CCR5-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response (2)confirmatory
504561A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 Fusion Inhibition Assay) - Dose Response (2)confirmatory
504563A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CXCR4-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response (2)confirmatory
504570A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 MAGI Antiviral Assay) - Dose Response (2)confirmatory
504571A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (HIV-1 PBMC Assay) - Cytotoxicity Counter Screen - Dose Response (2)confirmatory
504573A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 Fusion Inhibition Assay) - Secondary Cytotoxicity Screen (2)confirmatory
504574A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 Fusion Inhibition Assay) - Secondary Cytotoxicity Screen (2)confirmatory
504575A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen (2)confirmatory
504576A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen (4)confirmatory
504625A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CXCR4-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response (3)confirmatory
504626A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CCR5-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response (3)confirmatory
504630A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (HIV-1 PBMC Assay) - Cytotoxicity Counter Screen - Dose Response (3)confirmatory
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Production Centers Network (MLPCN)
Grant Number: 1R21NS059403-01
Assay Provider: Dr. Miriam Gochin, Touro University-California, Vallejo, CA

The fusion-active conformation of the envelope protein gp41 of HIV-1 consists of an N-terminal trimeric alpha-helical coiled coil domain, and three anti-parallel C-terminal helices which fold down the grooves of the coiled coil to form a six-helix bundle. Disruption of the six-helix bundle is considered to be a key component of an effective non-peptide fusion inhibitor. This structure forms as a result of a conformational change in gp41, triggered by gp120 and co-receptor binding to host cell receptors. Prevention of six-helix bundle formation has been recognized as an important mechanism for viral fusion inhibition

A metallopeptide-based fluorescence assay has been developed to detect HIV-1 fusion inhibitors, by the screening of small molecules that bind to the hydrophobic pocket of gp41. The assay involves two peptides representing the inner N-terminal-heptad-repeat (HR1) coiled coil and the outer C-terminal-heptad-repeat (HR2) helical domains of the gp41 six-helix bundle which forms prior to fusion. The HR1 peptide is modified with a metal-ligated dye complex, which maintains structural integrity and permits association with a fluorescein-labeled HR2 peptide concomitant with fluorescence quenching. Compounds able to disrupt six-helix bundle formation can act as fusion inhibitors, and can be detected in the assay from an increase in the fluorescence that is correlated with compound's efficacy.
Protocol
Please see pertinent AIDs: 1986, 2279, 2286, 2644, 2649, 2788, 2812, 434967, 435029, 435031, 493095, 504341, 504352, 504363, 504367, 504388, 504393, 504394, 504395, 504484, 504503, 504530, 504551, 504553, 504560, 504561, 504563, 504570, 504571, 504573, 504574, 504575, 504576, 504625, 504626, 504630
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100. Testing has not progressed to the point where a probe molecule has been identified.
Additional Information
Grant Number: 1R21NS059403-01

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