Target Information
Target General Information | Top | |||||
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Target ID |
T85426
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Target Name |
Hepatitis B virus Capsid protein (HBV C)
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Synonyms |
Core antigen; Core protein; HBcAg; p21.5
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Gene Name |
HBV C
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
Function |
Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions.
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UniProt ID | ||||||
Sequence |
MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAIL
CWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQLLWFHISCLTFGRETVIEYLV SFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRE SQC Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 8 Clinical Trial Drugs | + | ||||
1 | ABI-H0731 | Drug Info | Phase 2 | Hepatitis B | [2] | |
2 | ABI-H2158 | Drug Info | Phase 2 | Hepatitis B | [3] | |
3 | JNJ-56136379 | Drug Info | Phase 2 | Hepatitis B | [4] | |
4 | A204 | Drug Info | Phase 1 | Hepatitis B virus infection | [5] | |
5 | ABI-H3733 | Drug Info | Phase 1 | Hepatitis B | [6] | |
6 | EDP-514 | Drug Info | Phase 1 | Chronic HBV infection | [7] | |
7 | RG7907 | Drug Info | Phase 1 | Hepatitis B | [8] | |
8 | ZM-H1505R | Drug Info | Phase 1 | Hepatitis B | [9] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 7 Inhibitor drugs | + | ||||
1 | ABI-H0731 | Drug Info | [10] | |||
2 | ABI-H2158 | Drug Info | [11] | |||
3 | JNJ-56136379 | Drug Info | [1] | |||
4 | ABI-H3733 | Drug Info | [11] | |||
5 | EDP-514 | Drug Info | [12] | |||
6 | RG7907 | Drug Info | [8] | |||
7 | ZM-H1505R | Drug Info | [13] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | A204 | Drug Info | [5] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: 1-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}-4-(1,1,3,3-tetramethylbutyl)benzene | Ligand Info | |||||
Structure Description | HBc-F97L premature secretion phenotype | PDB:7PZL | ||||
Method | Electron microscopy | Resolution | 2.80 Å | Mutation | Yes | [14] |
PDB Sequence |
MDIDPYKEFG
10 ATVELLSFLP20 SDFFPSVRDL30 LDTASALYRE40 ALESPEHCSP50 HHTALRQAIV 60 CWGELMTLAT70 WVGVNLEDPA80 SRDLVVSYVN90 TNMGLKFRQL100 LWFHISCLTF 110 GRETVIEYLV120 SFGVWIRTPP130 AYRPPNAPIL140 STL
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Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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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
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There is no similarity protein (E value < 0.005) for this target
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References | Top | |||||
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REF 1 | JNJ-56136379, an HBV Capsid Assembly Modulator, Is Well-Tolerated and Has Antiviral Activity in a Phase 1 Study of Patients With Chronic Infection. Gastroenterology. 2020 Aug;159(2):521-533.e9. | |||||
REF 2 | ClinicalTrials.gov (NCT03576066) A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection. U.S. National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT04398134) A Study of ABI-H2158-containing Regimens in Participants With Chronic Hepatitis B Virus Infection. U.S. National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT03361956) An Efficacy, Safety, and Pharmacokinetics Study of JNJ-56136379 in Participants With Chronic Hepatitis B Virus Infection. U.S. National Institutes of Health. | |||||
REF 5 | Clinical pipeline report, company report or official report of Klus Pharma | |||||
REF 6 | ClinicalTrials.gov (NCT04271592) A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABI-H3733 in Healthy Adults. U.S. National Institutes of Health. | |||||
REF 7 | ClinicalTrials.gov (NCT04470388) A Study of EDP-514 in Patients With Chronic Hepatitis B Virus Infection Who Are Not Currently on Treatment. U.S. National Institutes of Health. | |||||
REF 8 | Clinical pipeline report, company report or official report of Roche. | |||||
REF 9 | ClinicalTrials.gov (NCT04220801) A Study of Orally Administered ZM-H1505R to Evaluate Safety, Tolerability and Pharmacokinetics After Single and Multiple Ascending Doses in Healthy Participants. U.S. National Institutes of Health. | |||||
REF 10 | Safety, pharmacokinetics, and antiviral effects of ABI-H0731, a hepatitis B virus core inhibitor: a randomised, placebo-controlled phase 1 trial. Lancet Gastroenterol Hepatol. 2020 Feb;5(2):152-166. | |||||
REF 11 | Clinical pipeline report, company report or official report of Assembly Biosciences. | |||||
REF 12 | Clinical pipeline report, company report or official report of Enanta Pharmaceuticals. | |||||
REF 13 | Clinical pipeline report, company report or official report of Shanghai Zhimeng Biopharma. | |||||
REF 14 | Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97. Viruses. 2021 Oct 20;13(11):2115. |
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