Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFGZB6)

• DTT Name: Human immunodeficiency virus GAG protein (HIV gag)
• Synonyms: Pr55Gag; Gag polyprotein
• Gene Name: HIV gag
• DTT Type: Clinical trial target; [1]
• UniProt ID: GAG_HV1H2
• TTD ID: T93627
• Sequence:
  MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQI
  LGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAA
  DTGHSNQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGAT
  PQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTT
  STLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRF
  YKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKA
  RVLAEAMSQVTNSATIMMQRGNFRNQRKIVKCFNCGKEGHTARNCRAPRKKGCWKCGKEG
  HQMKDCTERQANFLGKIWPSYKGRPGNFLQSRPEPTAPPEESFRSGVETTTPPQKQEPID
  KELYPLTSLRSLFGNDPSSQ
• Function: Gag polyprotein: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi).
• Reactome Pathway:
  Budding and maturation of HIV virion (R-HSA-162588)
  Integration of provirus (R-HSA-162592)
  Early Phase of HIV Life Cycle (R-HSA-162594)
  Minus-strand DNA synthesis (R-HSA-164516)
  Plus-strand DNA synthesis (R-HSA-164525)
  2-LTR circle formation (R-HSA-164843)
  Binding and entry of HIV virion (R-HSA-173107)
  Membrane binding and targetting of GAG proteins (R-HSA-174490)
  Assembly Of The HIV Virion (R-HSA-175474)
  Integration of viral DNA into host genomic DNA (R-HSA-175567)
  Autointegration results in viral DNA circles (R-HSA-177539)
  APOBEC3G mediated resistance to HIV-1 infection (R-HSA-180689)
  Vpr-mediated nuclear import of PICs (R-HSA-180910)
  Uncoating of the HIV Virion (R-HSA-162585)

Molecular Interaction Atlas (MIA) of This DTT

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bevirimat	DML2D8Q	Human immunodeficiency virus infection	1C62	Phase 2	[1]
LIPO-5	DMWY0V1	Human immunodeficiency virus infection	1C62	Phase 2	[2]
Ad35-GRIN	DM4L28K	Human immunodeficiency virus infection	1C62	Phase 1/2	[3]
Ad35-GRIN/ENV	DMG82ZA	Human immunodeficiency virus infection	1C62	Phase 1	[3]
RVSVIN HIV-1 gag vaccine	DMYRPC8	Human immunodeficiency virus infection	1C62	Phase 1	[4]
TBC-M4	DM9CDPO	Human immunodeficiency virus infection	1C62	Phase 1	[5]

5 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK-732461	DMJ0ZB6	Human immunodeficiency virus infection	1C62	Discontinued in Phase 2	[6]
Gem 92	DM4ZDVY	Human immunodeficiency virus-1 infection	1C62	Discontinued in Phase 1	[7]
MPC-9055	DMCMNKV	Human immunodeficiency virus infection	1C62	Discontinued in Phase 1	[8]
PA-1050040	DMF4KPM	Human immunodeficiency virus infection	1C62	Discontinued in Phase 1	[9]
MPI-461359	DMAVD4Q	Human immunodeficiency virus infection	1C62	Terminated	[10]

References

• [1] Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site. Eur J Med Chem. 2013 Apr;62:453-65.
• [2] HIV specific responses induced in nonhuman primates with ANRS HIV-Lipo-5 vaccine combined with rMVA-HIV prime or boost immunizations. Vaccine. 2015 May 11;33(20):2354-9.
• [3] A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults. PLoS One. 2012;7(8):e41936.
• [4] Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections. J Infect Dis. 2011 Nov;204 Suppl 3:S1075-81.
• [5] A Phase 1 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 subtype C-modified vaccinia Ankara virus vaccine candidate in Indian volunteers. AIDS Res Hum Retroviruses. 2009 Nov;25(11):1107-16.
• [6] Preventive technologies, research toward a cure, and immune-based and gene therapies. HIV Treatment Bulletin. 30 June 2013.
• [7] Technology evaluation: GEM-92, Hybridon Inc. Curr Opin Mol Ther. 1999 Aug;1(4):521-3.
• [8] New Small-Molecule Inhibitor Class Targeting Human Immunodeficiency Virus Type 1 Virion Maturation . Antimicrob Agents Chemother. 2009 December; 53(12): 5080-5087.
• [9] US patent application no. 2015,0105,350, Combination therapy comprising tenofovir alafenamide hemifumarate and cobicistat for use in the treatment of viral infections.
• [10] Human Immunodeficiency Virus Gag and protease: partners in resistance. Retrovirology. 2012 Aug 6;9:63.