Preclinical toxicity test results of a new antiviral–immune-modulator compound consisting of flavonoid molecules (COVID-19 clinical trial preliminary data)

Download
100171.pdf
2022-01-01
Budak, Gürer
ÖZKAN, SEÇİL
BUDAK, Mehmet
Şeker, Tamay
MERYEMOĞLU, BAHAR
Miran, Şükran Selin
Çoban, Canan Çakır
Tarkun, Örkun
Show full item record
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
354
views
185
downloads
Aim: Isolated specific glycone–aglycone conjugated flavonoids which are investigated for their effect of bioavailability and molecular concentrations. The specific formula is then tested via in vitro and in vivo cytotoxicity tests. Methods: Considering the higher affinity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), quercetin, quercetin 3-sambubioside-3’-glucoside, luteolin, apigenin-7-4’alloside, kaempferol-7-O-glucoside, epicatechin-epigallocatechin-3-O-gallate, and hesperetin were selected to investigate the effects of a new combination of the formula. Specific chemical analyses, such as high-performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC–MS), quadrupole time of flight mass spectrometry (QTOF–MS) analysis and ultraviolet–visible (UV–VIS) spectrophotometry, were performed for molecular qualification and quantification. Results: In silico molecular docking analyses have shown that flavonoids can bind strongly to the spike protein and main protease of the SARS-CoV-2 virus. Flavonoids also have anti-inflammatory and immune-modulating activity by inhibiting cytokines. Although flavonoids may be a treatment alternative for coronavirus disease 2019 (COVID-19), an effective flavonoid compound has yet to be developed. The main problem here is that the absorption rate of flavonoids is very low (2–10%) in the intestines, and these compounds are metabolized rapidly. In contrast, according to recent literature, a conjugated flavonoid mixture is better absorbed in the small intestine, and its toxic effects are relatively fewer. Conclusions: It is found that the new formula has no cytotoxic or genotoxic effects. Furthermore, oral administrations of the new compound did not produce any toxicity symptoms or any mortality in male and female rats. The pre-clinical in vitro and in vivo toxicity test results indicated that the new flavonoid formula can be safely used for clinical trials.
SARS-CoV-2, COVID-19, polyphenols, flavonoids, antiviral, immune-modulator, pre-clinical tests
https://doi.org/10.37349/emed.2022.00071
https://hdl.handle.net/11511/96000
Exploration of Medicine
Test and Measurement Center In advanced Technologies (MERKEZ LABORATUVARI), Article

Suggestions

Microstructural, biological and mechanical investigations of hydroxyapatite-β-tricalcium phosphate composites doped with strontium and fluoride
Pourreza, Elmira; Evis, Zafer; Department of Engineering Sciences (2016)
The aim of this study was to investigate the microstructure, mechanical and biological properties of biphasic hydroxyapatite--Tricalcium phosphate (HT) and HT substituted with constant fluoride (F−) and varying strontium (Sr2+) amounts. All the samples were synthesized via precipitation method and sintered at 1100°C for 1 h. It was observed that the relative density of the sintered strontium and fluoride doped HT slightly increased. For microstructural analysis, X-ray diffraction (XRD), scanning electron m...
Intracellular alkaline proteases produced by thermoacidophiles: detection of protease heterogeneity by gelatin zymography and polymerase chain reaction (PCR)
Kocabıyık, Semra (2002-08-01)
In this study 24 thermoacidophilic archeal and bacterial strains isolated from hot-springs and hot-soils were screened for their ability to produce intracellular alkaline proteases. The protease activities of the strains, based on azocasein hydrolysis, showed a variation from 0.6 to 5.1 U. The cell extracts of three most potent producers were further examined and it was found that their proteases exhibited maximum activity at 60-70 degreesC and showed a pH Optimum over a range of pH 7.0-8.5. Gelatin zymogra...
Thermostability and regulation of Clostridium thermocellum L-lactate dehydrogenase expressed in Escherichia coli
Assa, P; Ozkan, M; Özcengiz, Gülay (2005-01-01)
In this study, L-lactate dehydrogenase (L-LDH) of Clostridium thermocellum previously cloned aid expressed in Escherichia coli FMJ39 was partially purified and characterised. Optimum temperature and pH of the enzyme were found as 50 degrees C and 7.5, respectively. Different concentrations of Mn2+ did not affect the enzyme activity. Addition of 20-30 mM Mg2+, or the other hand, increased the LDH activity by about 10%. Relatively high concentrations of NaCl (2 M), fructose-1,6-diphosphate (FDP, 5 mM), ATP (1...
Nitrate reductase and glutamate dehydrogenase activities of resistant and sensitive cultivars of wheat and barley under boron toxicity
Mahboobi, H; Yucel, M; Öktem, Hüseyin Avni (2002-01-01)
In this study, changes in activity of key enzymes of nitrogen assimilation, namely nitrate reductase and glutamate dehydrogenase upon boron (B) toxicity in wheat (Triticum aestivum) and barley (Hordeum vulgare) cultivars were investigated. Ten-day-old seedlings were exposed to 10 mM boric acid for a duration of five days. Plants growing on the nutrient solutions and receiving no excess B, were maintained as controls. All experiments were conducted on leaf and root tissues of control and B-treated seedlings ...
Prenatal exposure of diclofenac sodium alters the behavioral development of young Wistar rats
ELİBOL, BİRSEN; Ogur, Begum Aritan; Doğru, Havva (2019-01-01)
Diclofenac sodium (DS), a potent inhibitor of cyclooxygenase, reduces the release of arachidonic acid and formation of prostaglandins. Being a nonsteroid drug that shows antiinflammatory action, the possible side effects of fetal DS administration gain importance in public and medical applications. Herein, the effects of DS administration (1 mg/kg) during gestational days 5-20 were investigated on the performance of Wistar rat pups in a variety of behavioral tasks. Four-week-old pups were subjected to senso...
Citation Formats
G. Budak et al., “Preclinical toxicity test results of a new antiviral–immune-modulator compound consisting of flavonoid molecules (COVID-19 clinical trial preliminary data),” Exploration of Medicine, vol. 3, pp. 1–21, 2022, Accessed: 00, 2022. [Online]. Available: https://doi.org/10.37349/emed.2022.00071.
METU IIS - Integrated Information Service open@metu.edu.tr