Target Information

Target General Infomation
Target ID
T95678
Former ID
TTDS00175
Target Name
Influenza A virus M2 protein
Gene Name
M
Synonyms
M2 proton channel; Matrix protein M2; M
Target Type
Successful
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).
BioChemical Class
Influenza viruses matrix protein
Target Validation
T95678
UniProt ID
P06821
Sequence
MSLLTEVETPIRNEWGCRCNGSSDPLAIAANIIGILHLILWILDRLFFKCIYRRFKYGLK
GGPSTEGVPKSMREEYRKEQQSAVDADDGHFVSIELE
Structure
1MP6; 2KIH; 2KWX; 2L0J; 2RLF
Drugs and Mode of Action
Drug(s) Amantadine Drug Info Approved Influenza A infection [467472], [537115]
Rimantadine Drug Info Approved Influenza A infection [538530]
TCN-032 Drug Info Phase 2 Influenza virus [524110]
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 524110ClinicalTrials.gov (NCT01719874) Influenza Virus Challenge Study to Test Monoclonal Antibody TCN-032 as a Treatment for Influenza. U.S. National Institutes of Health.
Ref 537115Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84.
Ref 538530FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019649.
Ref 535075pH-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 535790Proton 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 535843Are the 2-isomers of the drug rimantadine active anti-influenza A agents? Antivir Chem Chemother. 2003 May;14(3):153-64.
Ref 535874Heterocyclic rimantadine analogues with antiviral activity. Bioorg Med Chem. 2003 Dec 1;11(24):5485-92.
Ref 536317Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25.
Ref 536654Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. Epub 2008 Feb 4.
Ref 537074Antiviral resistance of influenza A (H3N2) strains isolated in northern Greece between 2004 and 2007. Euro Surveill. 2009 Jan 29;14(4). pii: 19104.
Ref 537379Discovery 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.
Ref 544135Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses. Proc Natl Acad Sci U S A. 2010 July 13; 107(28): 12658-12663.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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