Target Information

Target General Information

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Target ID

T95678 (Former ID: TTDS00175)

Target Name

Influenza M2 protein (Influ M)

Synonyms

Matrix protein M2; M2 proton channel; M

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Gene Name

Influ M

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

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

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.

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BioChemical Class

Influenza viruses matrix protein

UniProt ID

M2_I34A1

Sequence

MSLLTEVETPIRNEWGCRCNGSSDPLAIAANIIGILHLILWILDRLFFKCIYRRFKYGLK
GGPSTEGVPKSMREEYRKEQQSAVDADDGHFVSIELE

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Drugs and Modes of Action

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Approved Drug(s)

[+] 2 Approved Drugs

Amantadine

Drug Info

Approved

Influenza A virus infection

[2], [3]

Rimantadine

Drug Info

Approved

Influenza A virus infection

[4]

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

TCN-032

Drug Info

Phase 2

Influenza virus infection

[5]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 13 Inhibitor drugs

Amantadine

Drug Info

[6], [7], [8], [9]

Rimantadine

Drug Info

[1]

2-(1-adamantyl) piperidine

Drug Info

[11], [12], [13]

2-(1-adamantyl) pyrrolidine

Drug Info

[11], [12], [13]

2-(1-adamantyl)-2-methyl-pyrrolidine

Drug Info

[11], [12], [13]

2-(2-adamantyl) piperidine

Drug Info

[11], [12], [13]

3-(2-adamantyl) pyrrolidine

Drug Info

[11], [12], [13]

B-Octylglucoside

Drug Info

[14]

Rimantadine isomer 1

Drug Info

[11], [12], [13]

Rimantadine isomer 2

Drug Info

[11], [12], [13]

Spiro[cyclopropane-1,2-adamantan]-2-amine

Drug Info

[11], [12], [13]

Spiro[piperidine-2,2-adamantane]

Drug Info

[11], [12], [13]

Spiro[pyrrolidine-2,2-adamantane]

Drug Info

[11], [12], [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

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 Profiles in Patients

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Drug Resistance
Mutation (DRM)

Drug Resistance Mutation Info

Target Affiliated Biological Pathways

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WikiPathways

[+] 1 WikiPathways

Influenza Life Cycle

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

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 2

URL: 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 3

Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84.

REF 4

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019649.

REF 5

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 6

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.

REF 7

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

REF 8

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 9

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 10

Human 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 11

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

REF 12

Heterocyclic rimantadine analogues with antiviral activity. Bioorg Med Chem. 2003 Dec 1;11(24):5485-92.

REF 13

Are the 2-isomers of the drug rimantadine active anti-influenza A agents Antivir Chem Chemother. 2003 May;14(3):153-64.

REF 14

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

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