Targeting Natural Plant Metabolites for Hunting SARS-CoV-2 Omicron BA.1 Variant Inhibitors: Extraction, Molecular Docking, Molecular Dynamics, and Physicochemical Properties Study.

(1) Background: SARS-CoV-2 Omicron BA.1 is the most common variation found in most countries and is responsible for 99% of cases in the United States. To overcome this challenge, there is an urgent need to discover effective inhibitors to prevent the emerging BA.1 variant. Natural products, particularly flavonoids, have had widespread success in reducing COVID-19 prevalence. (2) Methods: In the ongoing study, fifteen compounds were annotated from Echium angustifolium and peach (Prunus persica), which were computationally analyzed using various in silico techniques. Molecular docking calculations were performed for the identified phytochemicals to investigate their efficacy. Molecular dynamics (MD) simulations over 200 ns followed by molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) were performed to estimate the binding energy. Bioactivity was also calculated for the best components in terms of drug likeness and drug score. (3) Results: The data obtained from the molecular docking study demonstrated that five compounds exhibited remarkable potency, with docking scores greater than -9.0 kcal/mol. Among them, compounds 1, 2 and 4 showed higher stability within the active site of Omicron BA.1, with ΔGbinding values of -49.02, -48.07, and -67.47 KJ/mol, respectively. These findings imply that the discovered phytoconstituents are promising in the search for anti-Omicron BA.1 drugs and should be investigated in future in vitro and in vivo research.

Antihepatotoxic Effect and Metabolite Profiling of Panicum turgidum Extract via UPLC-qTOF-MS.

BACKGROUND: Panicum turgidum, desert grass, has not reported any detailed phytochemical or biological study as yet. OBJECTIVE: To establish P. turgidum secondary metabolite profile and to assess its antihepatotoxic effect. MATERIALS AND METHODS: Ultra-performance liquid chromatography (UPLC) coupled to quadrupole high-resolution time of flight mass spectrometry (qTOF-MS) was used for large-scale secondary metabolites profiling in P. turgidum extract, alongside assessing median lethal dose (LD50) and hepatoprotective effect against carbon tetrachloride (CCl4) intoxication. RESULTS: A total of 39 metabolites were identified with flavonoids as the major class present as O/C-glycosides of luteolin, apigenin, isorhamnetin and naringenin, most of which are first time to be reported in Panicum sp. Antihepatotoxic effect of P. turgidum crude extract was revealed via improving several biochemical marker levels and mitigation against oxidative stress in the serum and liver tissues, compared with CCl4 intoxicated group and further confirmed by histopathological examination. CONCLUSION: This study reveals that P. turgidum, enriched in C-flavonoids, presents a novel source of safe antihepatotoxic agents and further demonstrates the efficacy of UPLC-MS metabolomics in the field of natural products drug discovery. SUMMARY: UPLC coupled to qTOF-MS was used for large scale secondary metabolites profiling in P. turgidum.A total of 39 metabolites were identified with flavonoids amounting as the major metabolite class.Anti-hepatotoxic effect of P. turgidum extract was revealed via several biochemical markers and histopathological examination.This study reveals that P. turgidum, enriched in C-flavonoids, present a novel source of antihepatotoxic agents. Abbreviations used: UPLC: Ultra-performance liquid chromatography (UPLC), LD50: median lethal dose, MDA: malondialdehyde, GSH: glutathione reductase, CAT: catalase, SOD: superoxide dismutase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, ALP: alkaline phosphatase, TG: triglycerides.