Target Information
| Target General Information | Top | |||||
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| Target ID |
T86674
(Former ID: TTDC00002)
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| Target Name |
Influenza Hemagglutinin (Influ HA)
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| Synonyms |
Hemagglutinin
Click to Show/Hide
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| Gene Name |
Influ HA
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Virus infection [ICD-11: 1A24-1D9Z] | |||||
| 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.
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| BioChemical Class |
Influenza viruses hemagglutinin
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| UniProt ID | ||||||
| Sequence |
MKANLLVLLCALAAADADTICIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDSHNGKLCR
LKGIAPLQLGKCNIAGWLLGNPECDPLLPVRSWSYIVETPNSENGICYPGDFIDYEELRE QLSSVSSFERFEIFPKESSWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPKLKNS YVNKKGKEVLVLWGIHHPPNSKEQQNLYQNENAYVSVVTSNYNRRFTPEIAERPKVRDQA GRMNYYWTLLKPGDTIIFEANGNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLG AINSSLPYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGM IDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQFTAVGKEFNKLEKRM ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLESMGIYQILAIYSTVASSL VLLVSLGAISFWMCSNGSLQCRICI Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Arbidol | Drug Info | Approved | Virus infection | [2] | |
| Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
| 1 | CR8020 | Drug Info | Phase 2 | Influenza virus infection | [3] | |
| 2 | RG7745 | Drug Info | Phase 2 | Infectious disease | [4] | |
| 3 | VIS410 | Drug Info | Phase 2 | Influenza A virus infection | [5] | |
| 4 | A/Anhui/05 | Drug Info | Phase 1 | Influenza virus infection | [6] | |
| 5 | ND-1.1 | Drug Info | Phase 1 | Influenza virus infection | [7] | |
| 6 | VGX-3400 | Drug Info | Phase 1 | Influenza A virus H5N1 infection | [8] | |
| 7 | VIR-2482 | Drug Info | Phase 1 | Influenza A virus infection | [9] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 7 Inhibitor drugs | + | ||||
| 1 | Arbidol | Drug Info | [1], [10] | |||
| 2 | VIS410 | Drug Info | [13] | |||
| 3 | 2-tert-butylbenzene-1,4-diol | Drug Info | [18], [19], [20], [21], [22] | |||
| 4 | Alpha-D-Mannose | Drug Info | [23] | |||
| 5 | BMY-27709 | Drug Info | [19], [20], [21], [22] | |||
| 6 | CL 385319 | Drug Info | [19], [20], [21], [22] | |||
| 7 | Stachyflin | Drug Info | [19], [20], [21], [22] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | PXVX-0103 | Drug Info | [24] | |||
| 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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| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | ClinicalTrials.gov (NCT01992276) Assessment of Efficacy of CR8020 and CR6261, Monoclonal Antibodies, Against Influenza Infection. U.S. National Institutes of Health. | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038254) | |||||
| REF 5 | ClinicalTrials.gov (NCT02468115) Influenza Challenge Study of VIS410 in Healthy Volunteers. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT00912496) Booster Trial to 07-0019 With A/Anhui/05 With and Without MF59. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT01698060) Immunogenicity of ND1.1 by Delivery Directly to the Ileum. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT01142362) Study of VGX-3400X, H5N1 Avian Influenza Virus DNA Plasmid + Electroporation in Healthy Adults. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT04033406) Study of VIR-2482 in Healthy Volunteers. U.S. National Institutes of Health. | |||||
| REF 10 | Investigation of triazavirin antiviral activity against influenza A virus (H5N1) in cell culture. Antibiot Khimioter. 2007;52(11-12):18-20. | |||||
| REF 11 | 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. | |||||
| REF 12 | Clinical pipeline report, company report or official report of Roche. | |||||
| REF 13 | Clinical pipeline report, company report or official report of Visterra. | |||||
| REF 14 | 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. | |||||
| REF 15 | 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. | |||||
| REF 16 | Clinical pipeline report, company report or official report of Inovio Pharmaceuticals. | |||||
| REF 17 | Clinical pipeline report, company report or official report of Vir Biotechnology. | |||||
| REF 18 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 19 | 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. | |||||
| REF 20 | Novel stachyflin derivatives from Stachybotrys sp. RF-7260. Fermentation, isolation, structure elucidation and biological activities. J Antibiot (Tokyo). 2002 Mar;55(3):239-48. | |||||
| REF 21 | An 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 22 | Inhibition 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 23 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 24 | Company report (PaxVax) | |||||
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