Characterization, in-silico, and in-vitro study of a new steroid derivative from Ophiocoma dentata as a potential treatment for COVID-19

Abstract

The medicinal potential of marine invertebrates' bioactive components that may act as anti-COVID-19 demonstrated promising results. Ophiocoma dentata, which is common in the Red Sea, is one such source. Therefore, this study aimed to isolate a new compound from the brittle star, Ophiocoma dentata, and evaluate its efficacy as anti-COVID-19 in-silico and in-vitro. Standard procedures were followed in order to assess the isolated compound’s preliminary toxicity and anti-inflammatory properties. Computer virtual screening technology through molecular docking and ADMET studies was conducted as well as a new steroid derivative was isolated for the first time, named 5α-cholesta-4(27), 24-dien-3β, 23 β-diol. Investigation of the Anti-Covid-19 activity of the isolated compound using a Plaque reduction assay revealed 95% inhibition at a concentration of 5 ng/µl (12.48 µM). Moreover, this compound showed an IC50 of 11,350 ± 1500 ng/ml against the normal fibroblast cells, indicating its safety. Interestingly, this compound exhibited anti-inflammatory activity with an IC50 of 51.92 ± 0.03 μg/ml compared to a reference drug’s IC50 of 53.64 ± 0.01 μg/ml, indicating that this compound is a potent anti-inflammatory. In silico data have proved that the isolated compound is a promising viral inhibitor against SARS-CoV2 and is thus recommended as a future nature preventive and curative antiviral drug.

A Comprehensive In Silico Study of New Metabolites from Heteroxenia fuscescens with SARS-CoV-2 Inhibitory Activity

“…Interestingly, the three steroids that shared the stable binding had a characteristic hydroxylation pattern at positions 3, 5, and 6 in rings A and B. In addition, we have reported that the triterpene class of compounds, which is structurally related to compounds 5 , 7 , and 8 , is a promising scaffold to develop new M pro inhibitors [ 45 , 46 ].…”

Identifying Substructures That Facilitate Compounds to Penetrate the Blood–Brain Barrier via Passive Transport Using Machine Learning Explainer Models

“…56 The MultiTaskClassifier model is a fully connected deep residual network for multitask classification composed of preactivation residual blocks. Hyperparameterization for this first model was performed to optimize the best parameters, including layer size [256,256], [256,256,256], [256,256,256,256], dropout [0.0, 0.1], learning rate [0.005, 0.0035, 0.0025, 0.0010], number of epochs [5,10,20,30,40,50], momentum [0.0, 0.9], decay [0.0, 0.1], and batch size [32,64,128]. This was done using the GridHyperparamOpt optimizer, 67 the hyperparameter search method, 61 and the ROC-AUC metric.…”

Corticosteroids: A boon or bane for COVID-19 patients?

“…Ciclesonide is another inhaled corticosteroid which was tested in COVID-19 patients, but there are still insufficient evidences whether it is beneficial to COVID-19 patients or not [129] . Another new steroid 5α-cholesta-4(27),24-dien-3β,23β-diol was isolated from Ophiocoma dentata and studied against SARS-CoV-2 [130] . The invitro result shows that the new isolated steroid can are effective in 95% inhibition of the SARS-CoV-2 virus at 5 μg/ml concentration.…”