Target Information

Target General Infomation
Target ID
T86674
Former ID
TTDC00002
Target Name
Hemagglutinin
Gene Name
HA
Synonyms
Hemagglutinin HA1 chain; Hemagglutinin HA2 chain; HA
Target Type
Successful
Disease Infections disease [ICD10: A00-B99]
Influenza virus [ICD10: J11.1]
Influenza A virus H5N1 [ICD9: 487, 488; ICD10: J10, J11]
Viral infections [ICD9: 054.0, 054.1, 054.2, 054.3, 075, 771.2, 052, 053; ICD10: B01, B02, A60, B00, B27, G05.1, P35.2]
Unspecified [ICD code not available]
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 of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a 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.
BioChemical Class
Influenza viruses hemagglutinin
Target Validation
T86674
UniProt ID
P03437
Sequence
MKTIIALSYIFCLALGQDLPGNDNSTATLCLGHHAVPNGTLVKTITDDQIEVTNATELVQ
SSSTGKICNNPHRILDGIDCTLIDALLGDPHCDVFQNETWDLFVERSKAFSNCYPYDVPD
YASLRSLVASSGTLEFITEGFTWTGVTQNGGSNACKRGPGSGFFSRLNWLTKSGSTYPVL
NVTMPNNDNFDKLYIWGIHHPSTNQEQTSLYVQASGRVTVSTRRSQQTIIPNIGSRPWVR
GLSSRISIYWTIVKPGDVLVINSNGNLIAPRGYFKMRTGKSSIMRSDAPIDTCISECITP
NGSIPNDKPFQNVNKITYGACPKYVKQNTLKLATGMRNVPEKQTRGLFGAIAGFIENGWE
GMIDGWYGFRHQNSEGTGQAADLKSTQAAIDQINGKLNRVIEKTNEKFHQIEKEFSEVEG
RIQDLEKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEMNKLFEKTRRQLRENAEEMGN
GCFKIYHKCDNACIESIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDWILWISFAISC
FLLCVVLLGFIMWACQRGNIRCNICI
Drugs and Mode of Action
Drug(s) Arbidol Drug Info Approved Viral infections [551871]
CR8020 mab Drug Info Phase 2 Influenza virus [524539]
RG7745 Drug Info Phase 2 Infections disease [549487]
A/Anhui/05 Drug Info Phase 1 Influenza virus [522683]
ND-1.1 Drug Info Phase 1 Influenza virus [524082]
VGX-3400 Drug Info Phase 1 Influenza A virus H5N1 [523072]
Inhibitor 2-tert-butylbenzene-1,4-diol Drug Info [551374]
Alpha-D-Mannose Drug Info [551393]
Arbidol Drug Info [537138], [537338]
BMY-27709 Drug Info [535252], [535454], [536931], [538146]
CL 385319 Drug Info [535252], [535454], [536931], [538146]
Stachyflin Drug Info [535252], [535454], [536931], [538146]
TBHQ Drug Info [535252], [535454], [536931], [538146]
Modulator PXVX-0103 Drug Info
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
DRM DRM Info
References
Ref 522683ClinicalTrials.gov (NCT00912496) Booster Trial to 07-0019 With A/Anhui/05 With and Without MF59. U.S. National Institutes of Health.
Ref 523072ClinicalTrials.gov (NCT01142362) Study of VGX-3400X, H5N1 Avian Influenza Virus DNA Plasmid + Electroporation in Healthy Adults. U.S. National Institutes of Health.
Ref 524082ClinicalTrials.gov (NCT01698060) Immunogenicity of ND1.1 by Delivery Directly to the Ileum. U.S. National Institutes of Health.
Ref 524539ClinicalTrials.gov (NCT01992276) Assessment of Efficacy of CR8020 and CR6261, Monoclonal Antibodies, Against Influenza Infection. U.S. National Institutes of Health.
Ref 549487Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038254)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 532121An 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.
Ref 532953Characterization 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.
Ref 535252An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology. Bioorg Med Chem Lett. 2001 Sep 3;11(17):2393-6.
Ref 535454Novel stachyflin derivatives from Stachybotrys sp. RF-7260. Fermentation, isolation, structure elucidation and biological activities. J Antibiot (Tokyo). 2002 Mar;55(3):239-48.
Ref 536931Structure 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. Epub 2008 Nov 12.
Ref 537138Investigation of triazavirin antiviral activity against influenza A virus (H5N1) in cell culture. Antibiot Khimioter. 2007;52(11-12):18-20.
Ref 537338Pharmacokinetic 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.
Ref 538146Inhibition of influenza A virus replication by compounds interfering with the fusogenic function of the viral hemagglutinin. J Virol. 1999 Jan;73(1):140-51.
Ref 544221A 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.
Ref 551031Clinical pipeline report, company report or official report of Inovio Pharmaceuticals.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551599Clinical pipeline report, company report or official report of Roche.

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