General Information of Drug Therapeutic Target (DTT) (ID: TTTWS2G)

DTT Name Human immunodeficiency virus Capsid p24 (HIV p24)
Synonyms CA
Gene Name HIV p24
DTT Type
Clinical trial target
[1]
UniProt ID
POL_HV1B1
TTD ID
T23343
Sequence
PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVG
GHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTN
NPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQE
VKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL
Function
Integrase: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre- integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This processis mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Lenacapavir DMW7TZV Human immunodeficiency virus-1 infection 1C62 Approved [2]
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4 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
F4co vaccine DM6UQNW Human immunodeficiency virus infection 1C62 Phase 2 [1]
Vacc-4x DMDAKZW Human immunodeficiency virus-1 infection 1C62 Phase 2 [3]
VH4004280 DMM5L3S Human immunodeficiency virus infection 1C62 Phase 1 [4]
VH4011499 DM1GSSM Human immunodeficiency virus infection 1C62 Phase 1 [4]
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References

1 EP patent application no. 2621528, Vaccine.
2 Clinical pipeline report, company report or official report of Gilead Sciences.
3 Clinical pipeline report, company report or official report of Bionor Pharma.
4 Clinical pipeline report, company report or official report of ViiV Healthcare