Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWORX6)

• DTT Name: Influenza Polymerase acidic endonuclease (Influ PA)
• Synonyms: RNA-directed RNA polymerase subunit P2; Polymerase acidic protein
• Gene Name: Influ PA
• DTT Type: Successful target; [1]
• UniProt ID: PA_I34A1
• TTD ID: T32369
• EC Number: EC 3.1.-.-
• Sequence:
  MEDFVRQCFNPMIVELAEKTMKEYGEDLKIETNKFAAICTHLEVCFMYSDFHFINEQGES
  IIVELGDPNALLKHRFEIIEGRDRTMAWTVVNSICNTTGAEKPKFLPDLYDYKENRFIEI
  GVTRREVHIYYLEKANKIKSEKTHIHIFSFTGEEMATKADYTLDEESRARIKTRLFTIRQ
  EMASRGLWDSFRQSERGEETIEERFEITGTMRKLADQSLPPNFSSLENFRAYVDGFEPNG
  YIEGKLSQMSKEVNARIEPFLKTTPRPLRLPNGPPCSQRSKFLLMDALKLSIEDPSHEGE
  GIPLYDAIKCMRTFFGWKEPNVVKPHEKGINPNYLLSWKQVLAELQDIENEEKIPKTKNM
  KKTSQLKWALGENMAPEKVDFDDCKDVGDLKQYDSDEPELRSLASWIQNEFNKACELTDS
  SWIELDEIGEDVAPIEHIASMRRNYFTSEVSHCRATEYIMKGVYINTALLNASCAAMDDF
  QLIPMISKCRTKEGRRKTNLYGFIIKGRSHLRNDTDVVNFVSMEFSLTDPRLEPHKWEKY
  CVLEIGDMLIRSAIGQVSRPMFLYVRTNGTSKIKMKWGMEMRRCLLQSLQQIESMIEAES
  SVKEKDMTKEFFENKSETWPIGESPKGVEESSIGKVCRTLLAKSVFNSLYASPQLEGFSA
  ESRKLLLIVQALRDNLEPGTFDLGGLYEAIEECLINDPWVLLNASWFNSFLTHALS
• Function: Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.
• Reactome Pathway:
  Transport of Ribonucleoproteins into the Host Nucleus (R-HSA-168271)
  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)
  Viral Messenger RNA Synthesis (R-HSA-168325)
  Viral RNP Complexes in the Host Cell Nucleus (R-HSA-168330)
  NEP/NS2 Interacts with the Cellular Export Machinery (R-HSA-168333)
  Uncoating of the Influenza Virion (R-HSA-168336)
  vRNA Synthesis (R-HSA-192814)
  Viral mRNA Translation (R-HSA-192823)
  cRNA Synthesis (R-HSA-192869)
  vRNP Assembly (R-HSA-192905)
  Influenza Infection (R-HSA-168255)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Baloxavir marboxil	DM1UV7F	Influenza virus infection	1E30-1E32	Approved	[1]

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.