2007
DOI: 10.1128/aac.00879-06
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Efficacy of Delayed Treatment with ST-246 Given Orally against Systemic Orthopoxvirus Infections in Mice

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 (EC 50 ) of 0.48 M against CV, 0.05 M against VV, and 0.07 M 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 EC 50 of 41.1 M against CV and 29.2 M against VV, with selectivity indices of >7 and >10, respectively.… Show more

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Cited by 130 publications
(129 citation statements)
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“…In the ECTV/mousepox model, we and others have evaluated successful, delayed dosings with CMX001 and ST-246 (39,40). Further evaluation of dosing regimens would be a logical next step in evaluating drug efficacy against MPXV in C57BL/6 stat1 Ϫ/Ϫ mice.…”
Section: Discussionmentioning
confidence: 99%
“…In the ECTV/mousepox model, we and others have evaluated successful, delayed dosings with CMX001 and ST-246 (39,40). Further evaluation of dosing regimens would be a logical next step in evaluating drug efficacy against MPXV in C57BL/6 stat1 Ϫ/Ϫ mice.…”
Section: Discussionmentioning
confidence: 99%
“…Currently used poxviral therapeutics include cidofovir, a nucleotide analogue that successfully inhibits orthopoxvirus infections both in vivo and in vitro (7,38). Additionally, screening approaches have yielded other compounds that inhibit orthopoxvirus infection, including ST-246, which prevents successful virus formation and is effective in animal models (8,47), and mitoxantrone, an anticancer agent that inhibits a late-stage assembly step of vaccinia virus (15). Our data indicate that the treatment of orthopoxvirus-infected cells with proteasome inhibitors or an E1 inhibitor dramatically affects late gene expression, suggesting that proteasome inhibitors or E1 inhibitors could potentially be employed as antivirals.…”
Section: Discussionmentioning
confidence: 99%
“…The effective concentration of compound required to inhibit virus-induced cytopathic effect by 50% is less than 0.07 M and 0.04 M against six VARV strains and five MPXV strains, respectively (25). The potent, prophylactic or postexposure protective antiviral activity of ST-246 in vivo has been described by numerous investigators using multiple animal models of virulent OPXV illness (1,8,10,19,20,24,27). Although these studies document ST-246 as an effective antiviral drug for prophylactic or postexposure treatment of OPXV infections, they do not address potential human therapeutic use of ST-246, i.e., after definitive rash illness onset.…”
mentioning
confidence: 99%