Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTBYP1X)

• DTT Name: Human immunodeficiency virus Envelope glycoprotein gp120 (HIV gp120)
• Synonyms: Env polyprotein gp120 (33-511)
• Gene Name: HIV gp120
• DTT Type: Successful target; [1]
• UniProt ID: ENV_HV1H2
• TTD ID: T00972
• Sequence:
  AVGIGALFLGFLGAAGSTMGAASMTLTVQARQLLSGIVQQQNNLLRAIEAQQHLLQLTVW
  GIKQLQARILAVERYLKDQQLLGIWGCSGKLICTTAVPWNASWSNKSLEQIWNHTTWMEW
  DREINNYTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWFNITNWLWYIKLFIMIVGG
  LVGLRIVFAVLSIVNRVRQGYSPLSFQTHLPTPRGPDRPEGIEEEGGERDRDRSIRLVNG
  SLALIWDDLRSLCLFSYHRLRDLLLIVTRIVELLGRRGWEALKYWWNLLQYWSQELKNSA
  VSLLNATAIAVAEGTDRVIEVVQGACRAIRHIPRRIRQGLERILL
• 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
Fostemsavir	DM50ILT	Human immunodeficiency virus infection	1C62	Approved	[2]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AIDSVAX	DMS2WV3	Human immunodeficiency virus infection	1C62	Phase 3	[3]
Multi-envelope HIV vaccine	DMAGCHE	Human immunodeficiency virus infection	1C62	Phase 1	[4]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-488043	DMRPU10	Human immunodeficiency virus infection	1C62	Discontinued in Phase 2	[5]
Pro 542	DMLOGR3	Human immunodeficiency virus infection	1C62	Discontinued in Phase 2	[6]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-821385	DMNZG8T	Human immunodeficiency virus infection	1C62	Preclinical	[7]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CD4 red blood cell electroinsertion	DMIV82T	Discovery agent	N.A.	Investigative	[8]

References

• [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.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2020
• [3] 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.
• [4] An assessment of the role of chimpanzees in AIDS vaccine research. Altern Lab Anim. 2008 Sep;36(4):381-428.
• [5] 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.
• [6] 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.
• [7] Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution. PLoS Pathog. 2013 February; 9(2): e1003184.
• [8] 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.