In-vitro and in-silico anti-HSV-1 activity of a marine steroid from the jellyfish Cassiopea andromeda venom, By Amir Vazirizadeh

Research

Title	In-vitro and in-silico anti-HSV-1 activity of a marine steroid from the jellyfish Cassiopea andromeda venom
Type	Article
Keywords	Cassiopea andromeda,anti-HSV-1,Docking,Secondary metabolite,Thymidine kinase
Journal	MICROBIAL PATHOGENESIS
DOI	https://doi.org/10.1016/j.micpath.2023.106486
Researchers	Shakib Shamsian (First researcher) , Iraj Nabipour (Second researcher) , Gholamhossein Mohebbi (Third researcher) , neda baghban (Fourth researcher) , Masoud Zare (Fifth researcher) , Keivan Zandi (Not in first six researchers) , Amir Vazirizadeh (Not in first six researchers) , Ammar Maryamabadi (Not in first six researchers) , Cedric Delattre (Not in first six researchers)

Abstract

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.