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Sci Rep
2022 Oct 28;121:5846. doi: 10.1038/s41598-022-09809-2.
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Characterization, in-silico, and in-vitro study of a new steroid derivative from Ophiocoma dentata as a potential treatment for COVID-19.
Abd El Hafez MSM
,
AbdEl-Wahab MG
,
Seadawy MG
,
El-Hosseny MF
,
Beskales O
,
Saber Ali Abdel-Hamid A
,
El Demellawy MA
,
Ghareeb DA
.
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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.
Figure 1. 5α-cholesta-4(27), 24-dien-3β, 23 β-diol isolated from the brittle star (O. dentata).
Figure 2. Superimposition of the co-crystallized pose and the docking pose of the same ligands. (a) PRD_002214 of COVID-19 main protease, (b) SAM of NSP10, (c) F86 of RNA-dependent RNA polymerase.
Figure 3. Morphology of fibroblast cells; (a) Control cells, (b) Cells treated with 3.12 μg/ml, (c) 6.25 μg/ml, (d) 12.5 μg/ml of the isolated compound.
Figure 4. (a) 3D of the isolated compound docked into the active site of COVID-19 main protease. (b) 2D of the compound docked into the active site of COVID-19 main protease and superimposed with the co-crystallized ligand. (c) Mapping surface showing the compound occupying the active pocket of COVID-19 main protease.
Figure 5. (a) 3D of the compound docked into the active site of COVID-19 NSP10. (b) 2D of the compound docked into the active site of COVID-19 NSP10 and superimposed with the co-crystallized ligand. (c) Mapping surface showing the compound occupying the active pocket of COVID-19 NSP10.
Figure 6. (a) 3D of the isolated compound docked into the active site of COVID-19 RNA-dependent RNA polymerase. (b) 2D of the compound docked into the active site of COVID-19 RNA-dependent RNA polymerase and superimposed with the co-crystallized ligand. (c) Mapping surface demonstrating the compound occupying the active pocket of COVID-19 RNA-dependent RNA polymerase.
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