Abstract
Twelve polyhydroxylated sulfated steroids synthesized from a 5α-cholestane skeleton with different substitutions in C-2, C-3 and C-6 were evaluated for cytotoxicity and antiviral activity against herpes simplex virus (HSV) by a virus plaque reduction assay. Four compounds elicited a selective inhibitory effect against HSV. The disodium salt of 2β,3α-dihydroxy-6E-hydroximine-5α-cholestane-2,3-disulfate, named compound 7, was the most effective inhibitor of HSV-1, HSV-2 and pseudorabies virus (PrV) strains, including acyclovir-resistant variants, in human and monkey cell lines. Preliminary mechanistic studies demonstrated that compound 7 did not affect the initial steps of virus entry but inhibited a subsequent event in the infection process of HSV.
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This work was funded by grants from Agencia Nacional para la Promoción Científica y Tecnológica (ANPCyT, grant number 0506), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, grant number 11220090100071), and Universidad de Buenos Aires (grant numbers 00448 and 00404), Argentina. CSS, MSM and EBD are Research Members of CONICET.
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Supplementary Fig. 1 Dose-dependent plaque reduction of HSV-1 after treatment with compound 7. Vero cells were infected with HSV-1 strain F in the absence (VC: virus control) or presence of the indicated concentrations (µg/ml) of compound 7. Plaques were revealed after 48 h of incubation at 37 °C. (TIFF 3475 kb)
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Pujol, C.A., Sepúlveda, C.S., Richmond, V. et al. Polyhydroxylated sulfated steroids derived from 5α-cholestanes as antiviral agents against herpes simplex virus. Arch Virol 161, 1993–1999 (2016). https://doi.org/10.1007/s00705-016-2867-y
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DOI: https://doi.org/10.1007/s00705-016-2867-y