Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTG90S6)

• DTT Name: Human immunodeficiency virus Glycoprotein 41 (HIV gp41)
• Synonyms: Env polyprotein gp41 (33-511)
• Gene Name: HIV gp41
• DTT Type: Successful target; [1]
• UniProt ID: ENV_HV1H2
• TTD ID: T06770
• Sequence:
  KLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLVNVTEN
  FNMWKNDMVEQMHEDIISLWDQSLKPCVKLTPLCVSLKCTDLKNDTNTNSSSGRMIMEKG
  EIKNCSFNISTSIRGKVQKEYAFFYKLDIIPIDNDTTSYKLTSCNTSVITQACPKVSFEP
  IPIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVI
  RSVNFTDNAKTIIVQLNTSVEINCTRPNNNTRKRIRIQRGPGRAFVTIGKIGNMRQAHCN
  ISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFN
  STWFNSTWSTEGSNNTEGSDTITLPCRIKQIINMWQKVGKAMYAPPISGQIRCSSNITGL
  LLTRDGGNSNNESEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKR
• 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.

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enfuvirtide	DM7YPM1	Human immunodeficiency virus infection	1C62	Approved	[1]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sifuvirtide	DMMIWCE	Human immunodeficiency virus infection	1C62	Phase 3	[2]
ITV-1	DMCJX79	Human immunodeficiency virus infection	1C62	Phase 2	[3]
MaC46/M87o	DMIRG15	Human immunodeficiency virus-1 infection	1C62	Phase 1/2	[4]
T-1249	DMB2NP8	Human immunodeficiency virus infection	1C62	Phase 1/2	[5]
Combinectin	DMTLP1N	Human immunodeficiency virus infection	1C62	Phase 1	[6]
Gp41 HIV-1 vaccine	DM9JV80	Human immunodeficiency virus infection	1C62	Phase 1	[7]
Multi-envelope HIV vaccine	DMAGCHE	Human immunodeficiency virus infection	1C62	Phase 1	[8]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [2] Broad antiviral activity and crystal structure of HIV-1 fusion inhibitor sifuvirtide.J Biol Chem.2012 Feb 24;287(9):6788-96.
• [3] Clinical pipeline report, company report or official report of Immunotech Laboratories.
• [4] DOI: 10.1038/mt.sj.6300124
• [5] HIV entry inhibitors in clinical development. Curr Opin Pharmacol. 2002 Oct;2(5):523-8.
• [6] Clinical pipeline report, company report or official report of ViiV Healthcare.
• [7] Phase 1 safety and immunogenicity evaluation of ADVAX, a multigenic, DNA-based clade C/B' HIV-1 candidate vaccine. PLoS One. 2010 Jan 25;5(1):e8617.
• [8] An assessment of the role of chimpanzees in AIDS vaccine research. Altern Lab Anim. 2008 Sep;36(4):381-428.