Small molecular inhibitors of hedgehog protein signaling for treating or protecting against influenza infection
Small molecule inhibitors of Hh signaling could be supplied as pills, inhalers, or intravenously to 1) preventatively treat patients likely to have been exposed to influenza infection or 2) treat patients with infection who are suspected or known to be infected by the virus. This could provide a treatment that could be used either alone or in combination with existing drugs such as Tamiflu.
Researchers at UC San Diego, The University of Texas at Austin, and The Scripps Research Institute have demonstrated a new role for NS1 in modifying cell-cell signaling. This novel activity was identified by expressing NS1 in the Drosophila wing, which produced phenotypes similar to those caused by over-activation of a branch of the Hedgehog (Hh) signaling pathway. Genetic epistasis experiments indicate that NS1 carries out this function by acting at the level of Gli1/Ci, a key transcriptional mediator of the Hh pathway. They screened for NS1 mutants in which the Hh modulating activity was lost and identified a point mutation in NS1 that impairs this function and defines a novel interaction surface between NS1 and host factors. When this mutant was incorporated into a mouse-adapted viral strain, lethality of the virus increased and greater lung epithelial damage was observed, which could be partially rescued by treating the mice with an Hh antagonist. These results suggest that in addition to its multiple cell autonomous functions, NS1 also modifies communication between host cells, that paradoxically promotes host survival, perhaps thereby optimizing its likelihood for widespread propagation. This invention provides a novel intracellular target which is known to play an essential role in virulence of seasonal as well and highly virulent forms of influenza. Blocking essential host signaling systems such as the Hh pathways that are exploited by the pathogen may be more effective than vaccines and should complement or augment the efficacy of existing drugs acting on extracellular viral targets.
Patent Number: US8554446B2
Application Number: US13203793A
Inventor: Sano, Keisuke | Wakao, Kazuhiro | Nishikiori, Takashi | Watanabe, Takashi
Priority Date: 15 Apr 2009
Priority Number: US8554446B2
Application Date: 29 Aug 2011
Publication Date: 8 Oct 2013
IPC Current: G06F001900 | F01L000134 | F02D002800 | F02D004114 | F02M002506 | F02M002508 | F02M005100
US Class: 701104 | 123198DB | 123572 | 123698 | 123703 | 123704 | 701103 | 701109 | 701114
Assignee Applicant: Toyota Jidosha Kabushiki Kaisha,Toyota-shi
Title: Control apparatus for internal combustion engine including variable valve operating mechanism
Usefulness: Control apparatus for internal combustion engine including variable valve operating mechanism
Summary: Control apparatus of internal combustion engine.
Novelty: Control apparatus of internal combustion engine, has injection-quantity determination section that determines fuel injection quantity during valve reset operation based on estimated blow-by-gas density in intake passage of gas
Biomedical
Pathogen
9095579
Additional Technologies by these Inventors Tech ID/UC Case 22396/2010-150-0 Related Cases 2010-150-0
USA
