Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF4CAM)

• DTT Name: Influenza Hemagglutinin (Influ HA)
• Synonyms: Hemagglutinin
• Gene Name: Influ HA
• DTT Type: Successful target; [1]
• BioChemical Class: Influenza viruses hemagglutinin
• UniProt ID: HEMA_I34A1
• TTD ID: T86674
• Sequence:
  MKANLLVLLCALAAADADTICIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDSHNGKLCR
  LKGIAPLQLGKCNIAGWLLGNPECDPLLPVRSWSYIVETPNSENGICYPGDFIDYEELRE
  QLSSVSSFERFEIFPKESSWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPKLKNS
  YVNKKGKEVLVLWGIHHPPNSKEQQNLYQNENAYVSVVTSNYNRRFTPEIAERPKVRDQA
  GRMNYYWTLLKPGDTIIFEANGNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLG
  AINSSLPYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGM
  IDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQFTAVGKEFNKLEKRM
  ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC
  FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLESMGIYQILAIYSTVASSL
  VLLVSLGAISFWMCSNGSLQCRICI
• Function: Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization either through clathrin-dependent endocytosis or through clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.
• Reactome Pathway:
  Entry of Influenza Virion into Host Cell via Endocytosis (R-HSA-168275)
  Fusion of the Influenza Virion to the Host Cell Endosome (R-HSA-168288)
  Release (R-HSA-168298)
  Budding (R-HSA-168302)
  Packaging of Eight RNA Segments (R-HSA-168303)
  Assembly of Viral Components at the Budding Site (R-HSA-168316)
  Uncoating of the Influenza Virion (R-HSA-168336)
  Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus (R-HSA-168874)
  Viral mRNA Translation (R-HSA-192823)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Influenza Infection (R-HSA-168255)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arbidol	DMOQK8Z	Virus infection	1A24-1D9Z	Approved	[1]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CR8020	DMQ47U6	Influenza virus infection	1E30-1E32	Phase 2	[2]
RG7745	DMK5PYS	Infectious disease	1A00-CA43.1	Phase 2	[3]
VIS410	DM1G6ME	Influenza A virus infection	1E30	Phase 2	[4]
A/Anhui/05	DMGJ7A4	Influenza virus infection	1E30-1E32	Phase 1	[5]
ND-1.1	DMVQAEK	Influenza virus infection	1E30-1E32	Phase 1	[6]
VGX-3400	DMGMEH7	Influenza A virus H5N1 infection	1E30	Phase 1	[7]
VIR-2482	DM6LQIU	Influenza A virus infection	1E30	Phase 1	[8]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-tert-butylbenzene-1,4-diol	DMNXI1E	Discovery agent	N.A.	Investigative	[9]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[10]
BMY-27709	DMAMYWL	Discovery agent	N.A.	Investigative	[11]
CL 385319	DML8MSC	Discovery agent	N.A.	Investigative	[11]
PXVX-0103	DM2P0I4	Discovery agent	N.A.	Investigative	[12]
Stachyflin	DMIZESL	Discovery agent	N.A.	Investigative	[11]

References

• [1] Pharmacokinetic properties and bioequivalence of two formulations of arbidol: an open-label, single-dose, randomized-sequence, two-period crossover study in healthy Chinese male volunteers. Clin Ther. 2009 Apr;31(4):784-92.
• [2] Characterization of a broadly neutralizing monoclonal antibody that targets the fusion domain of group 2 influenza A virus hemagglutinin. J Virol. 2014 Dec;88(23):13580-92.
• [3] Clinical pipeline report, company report or official report of Roche.
• [4] Clinical pipeline report, company report or official report of Visterra.
• [5] A Human Antibody Recognizing a Conserved Epitope of H5 Hemagglutinin Broadly Neutralizes Highly Pathogenic Avian Influenza H5N1 Viruses. J Virol. 2012 March; 86(6): 2978-2989.
• [6] An adenovirus-based vaccine with a double-stranded RNA adjuvant protects mice and ferrets against H5N1 avian influenza in oral delivery models. Clin Vaccine Immunol. 2013 Jan;20(1):85-94.
• [7] Clinical pipeline report, company report or official report of Inovio Pharmaceuticals.
• [8] Clinical pipeline report, company report or official report of Vir Biotechnology.
• [9] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [11] Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion. Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17736-41.
• [12] Company report (PaxVax)