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Abstract
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In this study, we investigated the potential in vitro anti-HSV-1 activities of the Cassiopea andromeda jellyfish
tentacle extract (TE) and its fractions, as well as computational work on the thymidine kinase (TK) inhibitory
activity of the identified secondary metabolites. The LD50, secondary metabolite identification, preparative and
analytical chromatography, and in silico TK assessment were performed using the Spearman-Karber, GC-MS,
silica gel column chromatography, RP-HPLC, LC-MS, and docking methods, respectively. The antiviral activity of
TE and the two purified compounds Ca2 and Ca7 against HSV-1 in Vero cells was evaluated by MTT and RT-PCR
assays. The LD50 (IV, mouse) values of TE, Ca2, and Ca7 were 104.0 ± 4, 5120 ± 14, and 197.0 ± 7 (μg/kg),
respectively. They exhibited extremely effective antiviral activity against HSV-1. The CC50 and MNTD of TE, Ca2,
and Ca7 were (125, 62.5), (25, 12.5), and (50, 3.125) μg/ml, respectively. GC-MS analysis of the tentacle extract
revealed seven structurally distinct chemical compositions. Four of the seven compounds had a steroid structure.
According to the docking results, all compounds showed binding affinity to the active sites of both thymidine
kinase chains. Among them, the steroid compound Pregn-5-ene-3,11-dione, 17,20:20,21 bis [methylenebis
(oxy)]-, cyclic 3-(1,2-ethane diyl acetal) (Ca2) exhibited the highest affinity for both enzyme chains, surpassing
that of standard acyclovir. In silico data confirmed the experimental results. We conclude that the oxosteroid Ca2
may act as a potent agent against HSV-1.
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