Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTM42UJ)

• DTT Name: Hepatitis B virus Capsid protein (HBV C)
• Synonyms: Core antigen; Core protein; HBcAg; p21.5
• Gene Name: HBV C
• DTT Type: Clinical trial target; [1]
• UniProt ID: CAPSD_HBVD3
• TTD ID: T85426
• Sequence:
  MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAIL
  CWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQLLWFHISCLTFGRETVIEYLV
  SFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRE
  SQC
• 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.

Molecular Interaction Atlas (MIA) of This DTT

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABI-H0731	DMX1KDM	Hepatitis B	1E51	Phase 2	[2]
ABI-H2158	DM6X70G	Hepatitis B	1E51	Phase 2	[3]
JNJ-56136379	DM9RW6H	Hepatitis B	1E51	Phase 2	[1]
A204	DMF1LYP	Hepatitis B virus infection	1E51.0	Phase 1	[4]
ABI-H3733	DM4TN6W	Hepatitis B	1E51	Phase 1	[3]
EDP-514	DM8KRA3	Chronic HBV infection	1E51.0Z	Phase 1	[5]
RG7907	DMKVIS5	Hepatitis B	1E51	Phase 1	[6]
ZM-H1505R	DMX6AJ8	Hepatitis B	1E51	Phase 1	[7]

References

• [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.
• [2] 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.
• [3] Clinical pipeline report, company report or official report of Assembly Biosciences.
• [4] Clinical pipeline report, company report or official report of Klus Pharma
• [5] Clinical pipeline report, company report or official report of Enanta Pharmaceuticals.
• [6] Clinical pipeline report, company report or official report of Roche.
• [7] Clinical pipeline report, company report or official report of Shanghai Zhimeng Biopharma.