Abstract |
ST-246 was evaluated for activity against cowpox virus (CV), vaccinia virus (VV), and ectromelia virus (ECTV) and had an in vitro 50% effective concentration (EC50) of 0.48 microM against CV, 0.05 microM against VV, and 0.07 microM against ECTV. The selectivity indices were >208 and >2,000 for CV and VV, respectively. The in vitro antiviral activity of ST-246 was significantly greater than that of cidofovir, which had an EC50 of 41.1 microM against CV and 29.2 microM against VV, with selectivity indices of >7 and >10, respectively. ST-246 administered once daily by oral gavage to mice infected intranasally with CV beginning 4 h or delayed until 72 h postinoculation was highly effective when given for a 14-day duration using 100, 30, or 10 mg/kg of body weight. When 100 mg/kg of ST-246 was administered to VV-infected mice, a duration of 5 days was sufficient to significantly reduce mortality even when treatment was delayed 24 h postinoculation. Viral replication in liver, spleen, and kidney, but not lung, of CV- or VV-infected mice was reduced by ST-246 compared to levels for vehicle-treated mice. When 100 mg/kg of ST-246 was given once daily to mice infected by the intranasal route with ECTV, treatment for 10 days prevented mortality even when treatment was delayed up to 72 h after viral inoculation. Viral replication in target organs of ECTV-infected mice was also reduced.
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Authors | Debra C Quenelle, R M L Buller, Scott Parker, Kathy A Keith, Dennis E Hruby, Robert Jordan, Earl R Kern |
Journal | Antimicrobial agents and chemotherapy
(Antimicrob Agents Chemother)
Vol. 51
Issue 2
Pg. 689-95
(Feb 2007)
ISSN: 0066-4804 [Print] United States |
PMID | 17116683
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Benzamides
- Indoles
- Isoindoles
- tecovirimat
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Topics |
- Administration, Oral
- Animals
- Benzamides
(administration & dosage)
- Disease Models, Animal
- Female
- Indoles
(administration & dosage)
- Isoindoles
- Mice
- Organ Specificity
- Orthopoxvirus
(drug effects, physiology)
- Poxviridae Infections
(drug therapy)
- Time Factors
- Treatment Outcome
- Virus Replication
(drug effects)
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