Target Information

Target General Information

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Target ID

T93627 (Former ID: TTDI01920)

Target Name

Human immunodeficiency virus GAG protein (HIV gag)

Synonyms

Pr55Gag; Gag polyprotein

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Gene Name

HIV gag

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Human immunodeficiency virus disease [ICD-11: 1C60-1C62]

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).

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UniProt ID

GAG_HV1H2

Sequence

MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQI
LGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAA
DTGHSNQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGAT
PQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTT
STLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRF
YKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKA
RVLAEAMSQVTNSATIMMQRGNFRNQRKIVKCFNCGKEGHTARNCRAPRKKGCWKCGKEG
HQMKDCTERQANFLGKIWPSYKGRPGNFLQSRPEPTAPPEESFRSGVETTTPPQKQEPID
KELYPLTSLRSLFGNDPSSQ

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Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 6 Clinical Trial Drugs

Bevirimat

Drug Info

Phase 2

Human immunodeficiency virus infection

[2]

LIPO-5

Drug Info

Phase 2

Human immunodeficiency virus infection

[3]

Ad35-GRIN

Drug Info

Phase 1/2

Human immunodeficiency virus infection

[4]

Ad35-GRIN/ENV

Drug Info

Phase 1

Human immunodeficiency virus infection

[5]

RVSVIN HIV-1 gag vaccine

Drug Info

Phase 1

Human immunodeficiency virus infection

[6]

TBC-M4

Drug Info

Phase 1

Human immunodeficiency virus infection

[7]

Discontinued Drug(s)

[+] 5 Discontinued Drugs

GSK-732461

Drug Info

Discontinued in Phase 2

Human immunodeficiency virus infection

[8]

Gem 92

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus-1 infection

[9]

MPC-9055

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[10]

PA-1050040

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[11]

MPI-461359

Drug Info

Terminated

Human immunodeficiency virus infection

[12]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 4 Inhibitor drugs

Bevirimat

Drug Info

[1]

MPC-9055

Drug Info

[19]

PA-1050040

Drug Info

[20]

MPI-461359

Drug Info

[21]

Modulator

[+] 1 Modulator drugs

Gem 92

Drug Info

[18]

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Similarity Proteins

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Similarity Proteins

There is no similarity protein (E value < 0.005) for this target

Co-Targets

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Co-Targets

Co-Targets Info

Target Affiliated Biological Pathways		Top
Reactome	[+] 14 Reactome Pathways	+
1	Uncoating of the HIV Virion
2	Budding and maturation of HIV virion
3	Integration of provirus
4	Early Phase of HIV Life Cycle
5	Minus-strand DNA synthesis
6	Plus-strand DNA synthesis
7	2-LTR circle formation
8	Binding and entry of HIV virion
9	Membrane binding and targetting of GAG proteins
10	Assembly Of The HIV Virion
11	Integration of viral DNA into host genomic DNA
12	Autointegration results in viral DNA circles
13	APOBEC3G mediated resistance to HIV-1 infection
14	Vpr-mediated nuclear import of PICs
WikiPathways	[+] 2 WikiPathways	+
1	Host Interactions of HIV factors
2	HIV Life Cycle

References

Top

REF 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.

REF 2

ClinicalTrials.gov (NCT00967187) Safety and Efficacy Study of MPC-4326 for Treatment of Patients With HIV-1 Infection.. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT01492985) Lipopeptide Immunisation With GTU-multiHIV Trial. U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT02099994) Safety & Immunogenicity of HIV Vaccines in Healthy Kenyan Adults. U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT01496989) Safety and Immunogenicity Study of HIV-MAG Vaccine +/- IL-12 and Ad35-GRIN/ENV in HIV-uninfected Volunteers. U.S. National Institutes of Health.

REF 6

Attenuation of Recombinant Vesicular Stomatitis Virus-Human Immunodeficiency Virus Type 1 Vaccine Vectors by Gene Translocations and G Gene Truncation Reduces Neurovirulence and Enhances Immunogenicity in Mice. J. Virol. January 2008 vol. 82 no. 1 207-219.

REF 7

ClinicalTrials.gov (NCT00902824) Safety and Immunogenicity of TBC-M4, a MVA HIV Vaccine Alone or in a Prime-Boost Regimen With ADVAX DNA HIV Vaccine. U.S. National Institutes of Health.

REF 8

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027409)

REF 9

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008217)

REF 10

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027745)

REF 11

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025464)

REF 12

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028566)

REF 13

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.

REF 14

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.

REF 15

Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections. J Infect Dis. 2011 Nov;204 Suppl 3:S1075-81.

REF 16

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.

REF 17

Preventive technologies, research toward a cure, and immune-based and gene therapies. HIV Treatment Bulletin. 30 June 2013.

REF 18

Technology evaluation: GEM-92, Hybridon Inc. Curr Opin Mol Ther. 1999 Aug;1(4):521-3.

REF 19

New Small-Molecule Inhibitor Class Targeting Human Immunodeficiency Virus Type 1 Virion Maturation . Antimicrob Agents Chemother. 2009 December; 53(12): 5080-5087.

REF 20

US patent application no. 2015,0105,350, Combination therapy comprising tenofovir alafenamide hemifumarate and cobicistat for use in the treatment of viral infections.

REF 21

Human Immunodeficiency Virus Gag and protease: partners in resistance. Retrovirology. 2012 Aug 6;9:63.

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