Purpose A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy. Methods First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs. Results The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo. Conclusion The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo .
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.
Hepatitis C virus (HCV) is an infectious disease that has become a global clinical issue because of its significant morbidity and mortality. Novel anti‐hepatitis C drugs are continuously developed to decrease the pervasiveness of the infection globally. A synthetic ravidasvir, benzimidazole‐naphthylene‐imidazole derivatives, has been used as an anti‐HCV drug. This study determined the metabolites of ravidasvir and its pharmacokinetics in rats using information‐dependent acquisition and multiple reaction monitoring scanning modes in linear ion trap LC–MS/MS instrument, respectively. Two time‐programming linear‐gradient chromatographic methods were employed using a Kinetex C18 column (50 × 3 mm, 2.6 μm) and a Luna HILIC column (100 × 4.6 mm, 3 μm) for the qualitative and quantitative determination of ravidasvir and its metabolites, respectively. In silico prediction where sites in a molecule are susceptible to metabolism by cytochrome P450 was implemented, which helped in proposing the metabolic pathway of ravidasvir. The most dominant metabolite in rat liver microsomal samples was oxidative ravidasvir, where one O‐demethylated metabolite and eight isomers of the oxidative ravidasvir metabolites were identified. The study provides essential data for proposing the metabolic pathway and successfully applied it to determine the pharmacokinetics of ravidasvir in rat plasma.
Colonic epithelium composes of various cell types including alkaline phosphate-expressing absorptive, mucussecreting goblet and neuroendocrine cells that are derived from stem cells through asymmetric division. The continuous renewal of stem cells occurs under the highly coordinated cellular redox state. In the current study, based on a comparison with other culture media, colon epithelial cells were able to be sustained in vitro with normal status for more than two months under the chosen culture condition; α-MEM medium containing 20% fetal bovine serum. The cultured epithelial cells had normal doubling time and normal morphological characteristics as examined by transmission electron microscope. Also, these cultured cells contained functional stem cells and maintained their differentiation potency of colon stem cells, compared with freshly isolated mucosal epithelial cells, as indicated by the maintaining of aldehyde dehydrogenase 1B1 expression (11.31 ± 0.45 to 11.15 ± 0.48), ability to reduce silver nitrate, alkaline phosphate activity (0.513 ± 0.007 mU/μg to 0.438 ± 0.005 mU/μg), mucin secretion (34.71 ± 0.714 μg/ml to 32.93 ± 0.357 μg/ml) in appropriate cellular redox state level (-258.4 ± 1.3 mV to -237.4 ± 3.7 mV). The present study showed sustaining replication potential and functional differentiation of colonic epithelial stem cell population in this culture. The above culture system may be useful as an in vitro model for stemness, toxicological, and carcinogenesis studies.
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