Target Information

Target General Information

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Target ID

T31595 (Former ID: TTDS00174)

Target Name

Influenza Neuraminidase (Influ NA)

Synonyms

STNA; NEU1; NANase; N-acylneuraminate glycohydrolase; Influ Sialidase

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Gene Name

Influ NA

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Influenza [ICD-11: 1E30-1E32]

Function

Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious.

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BioChemical Class

Glycosylase

UniProt ID

NRAM_I33A0

EC Number

EC 3.2.1.18

Sequence

MNPNQKIITIGSICMVVGIISLILQIGNIISIWISHSIQTGNQNHTGICNQGIITYNVVA
GQDSTSVILTGNSSLCPIRGWAIHSKDNGIRIGSKGDVFVIREPFISCSHLECRTFFLTQ
GALLNDKHSNGTVKDRSPYRALMSCPVGEAPSPYNSRFESVAWSASACHDGMGWLTIGIS
GPDNGAVAVLKYNGIITETIKSWRKKILRTQESECTCVNGSCFTIMTDGPSNGLASYKIF
KIEKGKVTKSIELNAPNSHYEECSCYPDTGKVMCVCRDNWHGSNRPWVSFDQNLDYQIGY
ICSGVFGDNPRPKDGPGSCGPVSADGANGVKGFSYRYGNGVWIGRTKSDSSRHGFEMIWD
PNGWTETDSRFSVRQDVVAMTDRSGYSGSFVQHPELTGLDCMRPCFWVELIRGRPEEETI
WTSGSIISFCGVNSDTVDWSWPDGAELPFTIDK

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Drugs and Modes of Action

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Approved Drug(s)

[+] 3 Approved Drugs

Oseltamivir

Drug Info

Approved

Influenza virus infection

[2]

Peramivir

Drug Info

Approved

Influenza virus infection

[3]

Zanamivir

Drug Info

Approved

Influenza virus infection

[2], [4]

Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

CS-8958

Drug Info

Phase 3

Influenza virus infection

[5]

UX-001

Drug Info

Phase 3

Hereditary inclusion body myositis

[6]

DAS-181

Drug Info

Phase 2

Influenza virus infection

[7]

Discontinued Drug(s)

[+] 2 Discontinued Drugs

BCX-140

Drug Info

Terminated

Influenza virus infection

[8]

GS-3435

Drug Info

Terminated

Influenza virus infection

[9]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 70 Inhibitor drugs

Oseltamivir

Drug Info

[10], [11]

Peramivir

Drug Info

[1], [10]

Zanamivir

Drug Info

[10], [11]

CS-8958

Drug Info

[1]

UX-001

Drug Info

[12]

DAS-181

Drug Info

[7], [13]

BCX-140

Drug Info

[13], [14], [15]

(E,E)-1,7-Diphenyl-4,6-heptadien-3-one

Drug Info

[17]

(E,E)-5-Hydroxy-1,7-diphenyl-4,6-heptadien-3-one

Drug Info

[17]

(S)-1,7-Diphenyl-6(E)-hepten-3-ol

Drug Info

[17]

2,4-Deoxy-4-Guanidino-5-N-Acetyl-Neuraminic Acid

Drug Info

[15]

2-Deoxy-2,3-Dehydro-N-Acetyl-Neuraminic Acid

Drug Info

[12]

4-(Acetylamino)-3-Amino Benzoic Acid

Drug Info

[12]

4-(ACETYLAMINO)-3-HYDROXY-5-NITROBENZOIC ACID

Drug Info

[18]

4-(ACETYLAMINO)-5-AMINO-3-HYDROXYBENZOIC ACID

Drug Info

[18]

4-Amino-2-Deoxy-2,3-Dehydro-N-Neuraminic Acid

Drug Info

[15]

8-DEOXYGARTANIN

Drug Info

[19]

A-192558

Drug Info

[20], [21], [22]

A-315675

Drug Info

[20], [21], [22]

Alpha-D-Mannose

Drug Info

[12]

APIGENIN

Drug Info

[23]

BCX-1827

Drug Info

[20], [21], [22]

BCX-1898

Drug Info

[20], [21], [22]

BCX-1923

Drug Info

[20], [21], [22]

Beta-D-Mannose

Drug Info

[12]

CALOPOCARPIN

Drug Info

[24]

Cristacarpin

Drug Info

[24]

CUDRATRICUSXANTHONE

Drug Info

[25]

Cudratricusxanthone F

Drug Info

[25]

Cudraxanthone D

Drug Info

[25]

Cudraxanthone L

Drug Info

[25]

Cudraxanthone M

Drug Info

[25]

Cyclopentane amide derivatives 1

Drug Info

[20], [21], [22]

Cyclopentane amide derivatives 2

Drug Info

[20], [21], [22]

Cyclopentane amide derivatives 3

Drug Info

[20], [21], [22]

Cyclopentane amide derivatives 4

Drug Info

[20], [21], [22]

DEMETHYLMEDICARPIN

Drug Info

[24]

ERYSTAGALLIN A

Drug Info

[24]

Erysubin D

Drug Info

[24]

Erysubin E

Drug Info

[24]

Erythribyssin D

Drug Info

[24]

Erythribyssin L

Drug Info

[24]

Erythribyssin M

Drug Info

[24]

Erythribyssin O

Drug Info

[24]

Eryvarin D

Drug Info

[24]

FANA

Drug Info

[20], [21], [22]

Fucose

Drug Info

[12]

Gamma-mangostin

Drug Info

[19]

GARCINONE D

Drug Info

[19]

GARTANIN

Drug Info

[19]

GOSSYPETIN

Drug Info

[23]

GS4071

Drug Info

[20], [21], [22]

HERBACETIN

Drug Info

[23]

ISONEORAUTENOL

Drug Info

[24]

KAEMPFEROL

Drug Info

[23]

KATSUMADAIN A

Drug Info

[17]

Lactose

Drug Info

[12]

MACLURAXANTHONE

Drug Info

[25]

MANGIFERIN

Drug Info

[25]

MANGOSTANIN

Drug Info

[19]

MANGOSTANOL

Drug Info

[19]

MANGOSTENONE F

Drug Info

[19]

MANGOSTENONE G

Drug Info

[19]

MANGOSTIN

Drug Info

[19]

NEORAUTENOL

Drug Info

[24]

O-Sialic Acid

Drug Info

[18]

PHASEOLIN

Drug Info

[24]

PHASEOLLIDIN

Drug Info

[24]

RHODIOLININ

Drug Info

[23]

SMEATHXANTHONE A

Drug Info

[19]

Modulator

[+] 1 Modulator drugs

GS-3435

Drug Info

[16], [13]

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

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

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 Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Other glycan degradation

Target-Related Models and Studies

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Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

Developing new antiviral agents for influenza treatment: what does the future hold Clin Infect Dis. 2009 Jan 1;48 Suppl 1:S3-13.

REF 2

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 3

2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.

REF 4

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 5

ClinicalTrials.gov (NCT00803595) A Multinational Phase III Study of CS-8958 (MARVEL). U.S. National Institutes of Health.

REF 6

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 7

Inhibition of neuraminidase inhibitor-resistant influenza virus by DAS181, a novel sialidase fusion protein. PLoS One. 2009 Nov 6;4(11):e7838.

REF 8

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006335)

REF 9

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005196)

REF 10

Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102.

REF 11

Antiviral agents for influenza, hepatitis C and herpesvirus, enterovirus and rhinovirus infections. Med J Aust. 2001 Jul 16;175(2):112-6.

REF 12

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

REF 13

Neuraminidase inhibitors: zanamivir and oseltamivir. Ann Pharmacother. 2001 Jan;35(1):57-70.

REF 14

CN patent application no. 104447481, Benzoic acid thiourea anti-influenza virus compounds as well as preparation method and use thereof.

REF 15

DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.

REF 16

US patent application no. 2010,0081,713, Compositions and methods for treating viral infections.

REF 17

Antiviral potential and molecular insight into neuraminidase inhibiting diarylheptanoids from Alpinia katsumadai. J Med Chem. 2010 Jan 28;53(2):778-86.

REF 18

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

REF 19

Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia mangostana. Bioorg Med Chem. 2010 Sep 1;18(17):6258-64.

REF 20

Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25.

REF 21

Comparison of the anti-influenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo. Bioorg Med Chem. 2005 Jun 2;13(12):4071-7.

REF 22

Syntheses and neuraminidase inhibitory activity of multisubstituted cyclopentane amide derivatives. J Med Chem. 2004 Apr 8;47(8):1919-29.

REF 23

Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorg Med Chem. 2009 Oct 1;17(19):6816-23.

REF 24

Prenylated pterocarpans as bacterial neuraminidase inhibitors. Bioorg Med Chem. 2010 May 1;18(9):3335-44.

REF 25

Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata. Bioorg Med Chem. 2009 Apr 1;17(7):2744-50.

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