Target Information
Target General Infomation | |||||
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Target ID |
T95678
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Former ID |
TTDS00175
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Target Name |
Influenza A virus M2 protein
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Gene Name |
M
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Synonyms |
M2 proton channel; Matrix protein M2; M
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Target Type |
Successful
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Disease | Influenza A infection [ICD10: J10, J11] | ||||
Influenza virus [ICD10: J11.1] | |||||
Function |
Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation (By similarity).
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BioChemical Class |
Influenza viruses matrix protein
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Target Validation |
T95678
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UniProt ID | |||||
Sequence |
MSLLTEVETPIRNEWGCRCNGSSDPLAIAANIIGILHLILWILDRLFFKCIYRRFKYGLK
GGPSTEGVPKSMREEYRKEQQSAVDADDGHFVSIELE |
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Structure |
1MP6; 2KIH; 2KWX; 2L0J; 2RLF
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Drugs and Mode of Action | |||||
Inhibitor | 2-(1-adamantyl) piperidine | Drug Info | [535843], [535874], [536317] | ||
2-(1-adamantyl) pyrrolidine | Drug Info | [535843], [535874], [536317] | |||
2-(1-adamantyl)-2-methyl-pyrrolidine | Drug Info | [535843], [535874], [536317] | |||
2-(2-adamantyl) piperidine | Drug Info | [535843], [535874], [536317] | |||
3-(2-adamantyl) pyrrolidine | Drug Info | [535843], [535874], [536317] | |||
Amantadine | Drug Info | [535075], [535790], [536654], [537379] | |||
B-Octylglucoside | Drug Info | [551393] | |||
Rimantadine | Drug Info | [537074] | |||
Rimantadine isomer 1 | Drug Info | [535843], [535874], [536317] | |||
Rimantadine isomer 2 | Drug Info | [535843], [535874], [536317] | |||
Spiro[cyclopropane-1,2-adamantan]-2-amine | Drug Info | [535843], [535874], [536317] | |||
Spiro[piperidine-2,2-adamantane] | Drug Info | [535843], [535874], [536317] | |||
Spiro[pyrrolidine-2,2-adamantane] | Drug Info | [535843], [535874], [536317] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
DRM | DRM Info | ||||
Pathways | |||||
WikiPathways | Influenza Life Cycle | ||||
References | |||||
Ref 467472 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4128). | ||||
Ref 524110 | ClinicalTrials.gov (NCT01719874) Influenza Virus Challenge Study to Test Monoclonal Antibody TCN-032 as a Treatment for Influenza. U.S. National Institutes of Health. | ||||
Ref 535075 | pH-dependent tetramerization and amantadine binding of the transmembrane helix of M2 from the influenza A virus. Biochemistry. 2000 Nov 21;39(46):14160-70. | ||||
Ref 535790 | Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data. FEBS Lett. 2003 Sep 18;552(1):17-22. | ||||
Ref 535843 | Are the 2-isomers of the drug rimantadine active anti-influenza A agents? Antivir Chem Chemother. 2003 May;14(3):153-64. | ||||
Ref 535874 | Heterocyclic rimantadine analogues with antiviral activity. Bioorg Med Chem. 2003 Dec 1;11(24):5485-92. | ||||
Ref 536317 | Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25. | ||||
Ref 536654 | Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. Epub 2008 Feb 4. | ||||
Ref 537074 | Antiviral resistance of influenza A (H3N2) strains isolated in northern Greece between 2004 and 2007. Euro Surveill. 2009 Jan 29;14(4). pii: 19104. | ||||
Ref 537379 | Discovery of spiro-piperidine inhibitors and their modulation of the dynamics of the M2 proton channel from influenza A virus. J Am Chem Soc. 2009 Jun 17;131(23):8066-76. |
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