title: Evaluation of anti-influenza effects of camostat in mice infected with non-adapted human influenza viruses.
abstract: The anti-influenza effects of camostat, a serine protease inhibitor, on in vivo influenza infections were evaluated. Mice which received non-adapted human influenza viruses intranasally, developed a reproducible infection with very low mortality. The infection was readily detected by the recovery of the virus from an oropharyngeal swab. Five-week-old ICR mice received intraperitoneal injections of saline (control), amantadine (known positive drug), or camostat, after infection with influenza A/Taiwan/1/86 virus. Virus detection was performed on day 1, 2, 3, 5, and 7 of postinfection. Both camostat and amantadine were effective in ameliorating mouse influenza. On day 5, mice injected with camostat (45%) or amantadine (50%) showed a lower virus secreting rate than those receiving saline (90%). Additionally, camostat showed strong anti-influenza effects on an amantadine-resistant type A virus and a type B virus infection in vitro. The results show that blocking the hemagglutinin cleavage is an effective target for development of an anti-influenza agent. They also demonstrate that virus detection from the oropharynx of mice, infected with non-adapted virus, is a useful in vivo influenza model.
authors.affiliation: WHO National Influenza Center, NIH Korea, Seoul, South Korea.
authors.forename: M G
authors.initials: MG
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.forename: K Y
authors.initials: KY
authors.lastname: Park
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000222:Adaptation, Physiological; D000547:Amantadine / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D004341:Drug Evaluation; D004952:Esters; D005260:Female; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D009980:Influenza A virus / Q000187:drug effects*; D009981:Influenza B virus / Q000187:drug effects*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D017817:Nasal Lavage Fluid / Q000821:virology; D009960:Oropharynx / Q000473:pathology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology
chemical_list: D000998:Antiviral Agents; D004952:Esters; D006146:Guanidines; C034532:camostat; D016670:Gabexate; D000547:Amantadine