Target Information
Target General Information | Top | |||||
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Target ID |
T00972
(Former ID: TTDI01924)
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Target Name |
Human immunodeficiency virus Envelope glycoprotein gp120 (HIV gp120)
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Synonyms |
Env polyprotein gp120 (33-511)
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Gene Name |
HIV gp120
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Human immunodeficiency virus disease [ICD-11: 1C60-1C62] | |||||
Function |
Transmembrane protein gp41: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C- terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin- dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm.
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UniProt ID | ||||||
Sequence |
KLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLVNVTEN
FNMWKNDMVEQMHEDIISLWDQSLKPCVKLTPLCVSLKCTDLKNDTNTNSSSGRMIMEKG EIKNCSFNISTSIRGKVQKEYAFFYKLDIIPIDNDTTSYKLTSCNTSVITQACPKVSFEP IPIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVI RSVNFTDNAKTIIVQLNTSVEINCTRPNNNTRKRIRIQRGPGRAFVTIGKIGNMRQAHCN ISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFN STWFNSTWSTEGSNNTEGSDTITLPCRIKQIINMWQKVGKAMYAPPISGQIRCSSNITGL LLTRDGGNSNNESEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKR Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Fostemsavir | Drug Info | Approved | Human immunodeficiency virus infection | [2] | |
Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | AIDSVAX | Drug Info | Phase 3 | Human immunodeficiency virus infection | [3] | |
2 | Multi-envelope HIV vaccine | Drug Info | Phase 1 | Human immunodeficiency virus infection | [4] | |
Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
1 | BMS-488043 | Drug Info | Discontinued in Phase 2 | Human immunodeficiency virus infection | [5] | |
2 | Pro 542 | Drug Info | Discontinued in Phase 2 | Human immunodeficiency virus infection | [6] | |
Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
1 | PF-821385 | Drug Info | Preclinical | Human immunodeficiency virus infection | [7] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | Fostemsavir | Drug Info | [2] | |||
2 | PF-821385 | Drug Info | [12] | |||
Modulator | [+] 3 Modulator drugs | + | ||||
1 | BMS-488043 | Drug Info | [10] | |||
2 | Pro 542 | Drug Info | [11] | |||
3 | CD4 red blood cell electroinsertion | Drug Info | [13] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: 1-ETHOXY-2-(2-ETHOXYETHOXY)ETHANE | Ligand Info | |||||
Structure Description | Artificial HIV fusion inhibitor AP3 fused to the C-terminus of gp41 NHR | PDB:5CMZ | ||||
Method | X-ray diffraction | Resolution | 2.57 Å | Mutation | Yes | [14] |
PDB Sequence |
IVQQQNNLLR
12 AIEAQQHLLQ22 LTVWGIKQLQ32 ARILAVERYL42 KDQ
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Ligand Name: Phosphocholine | Ligand Info | |||||
Structure Description | crystal structure of LN01 Fab in complex with an HIV-1 gp41 peptide | PDB:6SNC | ||||
Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [15] |
PDB Sequence |
NWFDITNWLW
680 YIKLFIMIV
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Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
Click to View More Binding Site Information of This Target with Different Ligands |
Chemical Structure based Activity Landscape of Target | Top |
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References | Top | |||||
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REF 1 | In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068. Antimicrob Agents Chemother. 2012 Jul;56(7):3498-507. | |||||
REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2020 | |||||
REF 3 | ClinicalTrials.gov (NCT00006327) Effectiveness of AIDSVAX B/E Vaccine in Intravenous Drug Users in Bangkok, Thailand. U.S. National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT00187044) Evaluation of the Safety of a Polyvalent Virus in Healthy Adults. U.S. National Institutes of Health. | |||||
REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020278) | |||||
REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005801) | |||||
REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023943) | |||||
REF 8 | HIV gp120 vaccine - VaxGen: AIDSVAX, AIDSVAX B/B, AIDSVAX B/E, HIV gp120 vaccine - Genentech, HIV gp120 vaccine AIDSVAX - VaxGen, HIV vaccine AIDSVAX - VaxGen. Drugs R D. 2003;4(4):249-53. | |||||
REF 9 | An assessment of the role of chimpanzees in AIDS vaccine research. Altern Lab Anim. 2008 Sep;36(4):381-428. | |||||
REF 10 | The investigations on HIV-1 gp120 bound with BMS-488043 by using docking and molecular dynamics simulations.J Mol Model.2013 Feb;19(2):905-17. | |||||
REF 11 | Treatment of advanced human immunodeficiency virus type 1 disease with the viral entry inhibitor PRO 542. Antimicrob Agents Chemother. 2004 Feb;48(2):423-9. | |||||
REF 12 | Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog. 2013 February; 9(2): e1003184. | |||||
REF 13 | Red blood cells bearing CD4 bind to gp120 covered plates and aggregate with cells expressing gp120. J Acquir Immune Defic Syndr. 1990;3(11):1041-5. | |||||
REF 14 | Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy. Sci Rep. 2015 Aug 19;5:13028. | |||||
REF 15 | Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe. 2019 Nov 13;26(5):623-637.e8. |
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