Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTXT3PU)

• DTT Name: Influenza M2 protein (Influ M)
• Synonyms: Matrix protein M2; M2 proton channel; M
• Gene Name: Influ M
• DTT Type: Successful target; [1]
• BioChemical Class: Influenza viruses matrix protein
• UniProt ID: M2_I34A1
• TTD ID: T95678
• Sequence:
  MSLLTEVETPIRNEWGCRCNGSSDPLAIAANIIGILHLILWILDRLFFKCIYRRFKYGLK
  GGPSTEGVPKSMREEYRKEQQSAVDADDGHFVSIELE
• 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.
• Reactome Pathway:
  Entry of Influenza Virion into Host Cell via Endocytosis (R-HSA-168275)
  Fusion of the Influenza Virion to the Host Cell Endosome (R-HSA-168288)
  Release (R-HSA-168298)
  Budding (R-HSA-168302)
  Packaging of Eight RNA Segments (R-HSA-168303)
  Assembly of Viral Components at the Budding Site (R-HSA-168316)
  Uncoating of the Influenza Virion (R-HSA-168336)
  Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus (R-HSA-168874)
  Viral mRNA Translation (R-HSA-192823)
  Influenza Infection (R-HSA-168255)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amantadine	DMS3YE9	Influenza A virus infection	1E30	Approved	[2]
Rimantadine	DM5DWMU	Influenza A virus infection	1E30	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TCN-032	DM9PVNJ	Influenza virus infection	1E30-1E32	Phase 2	[3]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(1-adamantyl) piperidine	DM05OJD	Discovery agent	N.A.	Investigative	[4]
2-(1-adamantyl) pyrrolidine	DMMSFEU	Discovery agent	N.A.	Investigative	[4]
2-(1-adamantyl)-2-methyl-pyrrolidine	DMIGRMV	Discovery agent	N.A.	Investigative	[4]
2-(2-adamantyl) piperidine	DMP1KZW	Discovery agent	N.A.	Investigative	[4]
3-(2-adamantyl) pyrrolidine	DMS98WA	Discovery agent	N.A.	Investigative	[4]
B-Octylglucoside	DMMO75G	Discovery agent	N.A.	Investigative	[5]
Rimantadine isomer 1	DMN98U1	Discovery agent	N.A.	Investigative	[4]
Rimantadine isomer 2	DM3BEF7	Discovery agent	N.A.	Investigative	[4]
Spiro[cyclopropane-1,2-adamantan]-2-amine	DMGFC8D	Discovery agent	N.A.	Investigative	[4]
Spiro[piperidine-2,2-adamantane]	DMWU9PV	Discovery agent	N.A.	Investigative	[4]
Spiro[pyrrolidine-2,2-adamantane]	DMW48JD	Discovery agent	N.A.	Investigative	[4]

References

• [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.
• [2] 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.
• [3] 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.
• [4] Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.