Tecovirimat

Tecovirimat(ST-246) is an orally bioavailable antipoxvirus compound; potent and selective active against multiple orthopoxviruses with EC50 about 10 nM.IC50 value: 10 nM [1]Target: antipoxvirusin vitro: ST-246 targets the cowpox virus V061 gene, which encodes a major envelope protein homologous to the vaccinia virus F13L gene product. The antiviral potency and selectivity of ST-246 was measured in CPE assays against a panel of DNA- and RNA-containing viruses. In these assays, the EC50 for inhibition of vaccinia virus was determined to be 0.01 μM, while the EC50 values for inhibition of unrelated viruses were >40 μM [1]. 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 [2]. in vivo: Mice were treated with placebo (vehicle), ST-246 administered by oral gavage at 50 mg/kg twice a day (b.i.d.) for 14 days, or CDV administered as a single intraperitoneal (i.p.) injection at 100 mg/kg. ST-246-treated mice mounted a protective immune response to vaccinia virus infection [1]. 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 [2].

[1]. Yang G, et al. An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge. J Virol. 2005 Oct;79(20):13139-49. [2]. Quenelle DC, et al. Efficacy of delayed treatment with ST-246 given orally against systemic orthopoxvirus infections in mice. Antimicrob Agents Chemother. 2007 Feb;51(2):689-95.