title: Evaluation of orally delivered ST-246 as postexposure prophylactic and antiviral therapeutic in an aerosolized rabbitpox rabbit model.
abstract: Orthopoxviruses, such as variola and monkeypox viruses, can cause severe disease in humans when delivered by the aerosol route, and thus represent significant threats to both military and civilian populations. Currently, there are no antiviral therapies approved by the U.S. Food and Drug Administration (FDA) to treat smallpox or monkeypox infection. In this study, we showed that administration of the antiviral compound ST-246 to rabbits by oral gavage, once daily for 14 days beginning 1h postexposure (p.e.), resulted in 100% survival in a lethal aerosolized rabbitpox model used as a surrogate for smallpox. Furthermore, efficacy of delayed treatment with ST-246 was evaluated by beginning treatment on days 1, 2, 3, and 4 p.e. Although a limited number of rabbits showed less severe signs of the rabbitpox disease from the day 1 and day 2 p.e. treatment groups, their illness resolved very quickly, and the survival rates for these group of rabbits were 88% and 100%, respectively. But when the treatment was started on days 3 or 4 p.e., survival was 67% and 33%, respectively. This work suggests that ST-246 is a very potent antiviral compound against aerosolized rabbitpox in rabbits and should be investigated for further development for all orthopoxvirus diseases.
authors.affiliation: Center for Aerobiological Sciences, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, United States. aysegul.nalca@amedd.army.mil
authors.forename: Aysegul
authors.initials: A
authors.lastname: Nalca
authors.forename: Josh M
authors.initials: JM
authors.lastname: Hatkin
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Garza
authors.forename: Donald K
authors.initials: DK
authors.lastname: Nichols
authors.forename: Sarah W
authors.initials: SW
authors.lastname: Norris
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Hruby
authors.forename: Robert
authors.initials: R
authors.lastname: Jordan
mesh_terms: D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D005260:Female; D054833:Isoindoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008168:Lung / Q000473:pathology; D011817:Rabbits; D016019:Survival Analysis; D013997:Time Factors; D014615:Vaccinia / Q000517:prevention & control*; D014616:Vaccinia virus / Q000187:drug effects*; D010797:Phthalimides
chemical_list: D000336:Aerosols; D000998:Antiviral Agents; D001549:Benzamides; D054833:Isoindoles; C505045:tecovirimat; D010797:Phthalimides