Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT62KQV)

• DTT Name: Influenza Polymerase basic protein 2 (Influ PB2)
• Synonyms: RNA-directed RNA polymerase subunit P3; Polymerase basic protein 2
• Gene Name: Influ PB2
• DTT Type: Clinical trial target; [1]
• UniProt ID: PB2_I34A1
• TTD ID: T57654
• Sequence:
  MERIKELRNLMSQSRTREILTKTTVDHMAIIKKYTSGRQEKNPALRMKWMMAMKYPITAD
  KRITEMIPERNEQGQTLWSKMNDAGSDRVMVSPLAVTWWNRNGPITNTVHYPKIYKTYFE
  RVERLKHGTFGPVHFRNQVKIRRRVDINPGHADLSAKEAQDVIMEVVFPNEVGARILTSE
  SQLTITKEKKEELQDCKISPLMVAYMLERELVRKTRFLPVAGGTSSVYIEVLHLTQGTCW
  EQMYTPGGEVRNDDVDQSLIIAARNIVRRAAVSADPLASLLEMCHSTQIGGIRMVDILRQ
  NPTEEQAVDICKAAMGLRISSSFSFGGFTFKRTSGSSVKREEEVLTGNLQTLKIRVHEGY
  EEFTMVGRRATAILRKATRRLIQLIVSGRDEQSIAEAIIVAMVFSQEDCMIKAVRGDLNF
  VNRANQRLNPMHQLLRHFQKDAKVLFQNWGVEPIDNVMGMIGILPDMTPSIEMSMRGVRI
  SKMGVDEYSSTERVVVSIDRFLRIRDQRGNVLLSPEEVSETQGTEKLTITYSSSMMWEIN
  GPESVLVNTYQWIIRNWETVKIQWSQNPTMLYNKMEFEPFQSLVPKAIRGQYSGFVRTLF
  QQMRDVLGTFDTAQIIKLLPFAAAPPKQSRMQFSSFTVNVRGSGMRILVRGNSPVFNYNK
  ATKRLTVLGKDAGTLTEDPDEGTAGVESAVLRGFLILGKEDKRYGPALSINELSNLAKGE
  KANVLIGQGDVVLVMKRKRDSSILTDSQTATKRIRMAIN
• Function: Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex. In addition, participates in the inhibition of type I interferon induction through interaction with and inhibition of the host mitochondrial antiviral signaling protein MAVS.
• 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 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VX-787	DMM2JXP	Influenza A virus infection	1E30	Phase 3	[1]

References

• [1] Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J Med Chem. 2014 Aug 14;57(15):6668-78.