Anti-Influenza Virus Drug

Anti-influenza viral agents that specifically inhibit MTr1, a host enzyme essential for the influenza virus replication initiation process (cap snatching).

Advantages

  • Completely different target from conventional anti-influenza viral drugs, synergistic effect when used in combination.
  • This drug targets a host enzyme, making drug resistance less likely to

Background and Technology

In the replication of some virus families, a process called cap snatching is essential, in which a portion of the host RNA is hijacked to allow its own replication. Influenza A and B viruses (IAV and IBV) in particular require maturation of CAP RNA by MTr1 (2′-O-ribose methyltransferase 1) in the host before cap snatching can occur.
Conventional anti-influenza virus drugs have the weakness that they act directly on specific viral proteins, and thus drug resistance can easily emerge due to viral gene mutation. We screened for antiviral drugs that inhibit host MTr1 and suppress influenza virus replication and developed TMFT (trifluoromethyl-tubercidin, a natural product derivative from Streptomyces, shown left). TMFT inhibited IAV and IBV replication specifically and showed no cytotoxicity (center and right figures).

 

Reference and Patent

Principal Investigator

Manabu IGARASHI (Hokkaido University International Institute for Zoonosis Control)

Current Stage and Next Step

  • TFMT, a specific and non-toxic MTr1 inhibitor, was demonstrated to specifically inhibit replication of Cap Snatching-dependent viruses, IAV and IBV, and its mechanism was elucidated. We also confirmed its synergistic effect when used in combination with Xofluza, an existing anti-IAV drug.
  • Seeking partners interested in developing TMFT-based or Cap Snatching-targeted anti-IAV drugs.
  • Evaluations/feasibility study under a CDA, MTA, or research collaboration is available.

 

Project No. BK-04653

 

Medicine

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