Target Information

Target General Information

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Target ID

T86674 (Former ID: TTDC00002)

Target Name

Influenza Hemagglutinin (Influ HA)

Synonyms

Hemagglutinin

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Gene Name

Influ HA

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

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

UniProt ID

HEMA_I34A1

Sequence

MKANLLVLLCALAAADADTICIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDSHNGKLCR
LKGIAPLQLGKCNIAGWLLGNPECDPLLPVRSWSYIVETPNSENGICYPGDFIDYEELRE
QLSSVSSFERFEIFPKESSWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPKLKNS
YVNKKGKEVLVLWGIHHPPNSKEQQNLYQNENAYVSVVTSNYNRRFTPEIAERPKVRDQA
GRMNYYWTLLKPGDTIIFEANGNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLG
AINSSLPYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGM
IDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQFTAVGKEFNKLEKRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC
FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLESMGIYQILAIYSTVASSL
VLLVSLGAISFWMCSNGSLQCRICI

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Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

CR8020

Drug Info

Phase 2

Influenza virus infection

[4]

RG7745

Drug Info

Phase 2

Infectious disease

[5]

A/Anhui/05

Drug Info

Phase 1

Influenza virus infection

[7]

ND-1.1

Drug Info

Phase 1

Influenza virus infection

[8]

VGX-3400

Drug Info

Phase 1

Influenza A virus H5N1 infection

[9]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 4 Inhibitor drugs

2-tert-butylbenzene-1,4-diol

Drug Info

[15], [16], [17], [18], [19]

Alpha-D-Mannose

Drug Info

[20]

BMY-27709

Drug Info

[16], [17], [18], [19]

CL 385319

Drug Info

[16], [17], [18], [19]

Modulator

[+] 1 Modulator drugs

PXVX-0103

Drug Info

[21]

Different Human System Profiles of Target	Top
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

Different Human System Profiles of Target

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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

There is no similarity protein (E value < 0.005) for this target

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Drug Resistance
Mutation (DRM)

Drug Resistance Mutation Info

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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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 (NCT02468115) Influenza Challenge Study of VIS410 in Healthy Volunteers. U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT01992276) Assessment of Efficacy of CR8020 and CR6261, Monoclonal Antibodies, Against Influenza Infection. U.S. National Institutes of Health.

REF 5

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 6

ClinicalTrials.gov (NCT04033406) Study of VIR-2482 in Healthy Volunteers. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT00912496) Booster Trial to 07-0019 With A/Anhui/05 With and Without MF59. U.S. National Institutes of Health.

REF 8

ClinicalTrials.gov (NCT01698060) Immunogenicity of ND1.1 by Delivery Directly to the Ileum. U.S. National Institutes of Health.

REF 9

ClinicalTrials.gov (NCT01142362) Study of VGX-3400X, H5N1 Avian Influenza Virus DNA Plasmid + Electroporation in Healthy Adults. U.S. National Institutes of Health.

REF 10

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 11

Clinical pipeline report, company report or official report of Roche.

REF 12

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 13

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 14

Clinical pipeline report, company report or official report of Inovio Pharmaceuticals.

REF 15

The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

REF 16

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 17

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 18

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 19

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 20

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 21

Company report (PaxVax)

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