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Inhibiting α‐glucosidase, a key enzyme in carbohydrate hydrolysis, can potentially control diabetes mellitus. Although commercially available drugs effectively lower blood glucose levels to mitigate hyperglycemia, their associated gastrointestinal side effects necessitate the exploration of explicit inhibitors with minimal side effects. We studied a library of 80 secondary metabolites ascribed to their antidiabetic properties and screened the most potent inhibitors using a comprehensive in silico approach, including molecular docking, DFT study, MD simulation, PCA, MMPBSA calculation, and pharmacokinetic analysis. Scolopianate A and ponasterone A emerged as potent α‐glucosidase inhibitors, forming hydrogen bonds with the catalytic diad and exhibiting prominent binding affinities of −8 kcal/mol. Further analyses encompassed significant reactivity at the catalytic site and stable protein‐ligand complexes, as asserted by 100 ns RMSD, RMSF, Rg, SASA, H‐bond, and PCA‐based free energy landscape analysis. The subsequent analysis of MMPBSA indicating a higher binding free energy of these compounds compared to reference ligand, acarbose further strengthened the validity of these findings. Furthermore, drug‐like behavior and favorable ADMET profiles affirmed scolopianate A and ponasterone A as robust α‐glucosidase inhibitors. These findings highlight their promise for future drug development targeting α‐glucosidase inhibition in diabetes management; however, more research needs to be conducted. [ABSTRACT FROM AUTHOR]

Essential oils (EOs) from Citrus sinensis (Rutaceae) possess diverse biological activities. However, a comprehensive comparison of their chemical composition and bioactivity across different plant parts has not been studied yet. The current research comparatively assesses the yield, chemical composition, chiral distribution, antioxidant properties, and larvicidal activity of EOs extracted from the peels, leaves, and flowers of C. sinensis. EOs extracted via hydro-distillation (HD) and steam distillation (SD) were analyzed by gas chromatography–mass spectrometry (GC-MS) and chiral GC-MS to explore their chemical composition and enantiomeric distribution. In addition, their larvicidal and antioxidant potentials were evaluated following standard protocols. Peels of C. sinensis exhibited significantly higher oil content (1.75–2.25%) compared to its leaves (0.75–0.78%) and flowers (0.20–0.25%). The GC-MS analysis identified around 60 compounds, including terpenoids, sesquiterpenoids, and oxygenated terpenoids in the HD and SD extractions. Higher concentrations of sabinene were found in flower extract (38.05–39.89%) and leaf extract (32.30–36.91%), while peel extract contained more than 90% limonene. The larvicidal activity of peel oil was primarily attributed to limonene, with an LC50 value of 0.0031 µL/mL. The current study reports the first chiral (GC-MS) analysis in the essential oil of the leaves and flowers of C. sinensis, paving the way for authenticity and purity. Furthermore, the chemical profiling of citrus EOs, particularly from the peel, demonstrates a safe and promising candidate for diverse biological applications. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) underwent a substantial number of alterations, and the accompanying structural mutations in the spike protein prompted questions about the virus's propensity to evade the antibody neutralization produced by prior infection or vaccination. New mutations in SARS-CoV-2 have raised serious concerns regarding the effectiveness of drugs and vaccines against the virus; thus, identifying and developing potent antiviral medications is crucial to combat viral infections. In the present study, we conducted a detailed in silico investigation that involves molecular docking, density functional (DFT) analysis, molecular dynamics (MD) simulations, and pharmacological analysis followed by an in vitro study with the spike protein. Among fifty terpenes screened, cryptotanshinone and saikosaponin B2 were found to be potent S1-RBD spike protein inhibitors, displaying considerable hydrogen bond interactions with key binding site residues, significant binding affinity, and high reactivity attributed to band gap energy. In addition, 100 ns molecular dynamics (MD) simulations further substantiated these findings, showcasing the stability of the compounds within a biological environment. With favorable pharmacokinetic properties and a low half inhibitory concentration (IC50) of 86.06 ± 1.56 μM, cryptotanshinone inhibited S1-RBD of the SARS-CoV-2 Omicron variant. Our findings account for in-depth research on cryptotanshinone as a SARS-CoV-2 inhibitor. [ABSTRACT FROM AUTHOR]

Despite the rigorous global efforts to control SARS-CoV-2 transmission, it continues to pose a serious threat to humans with the frequent emergence of new variants. Thus, robust therapeutics to combat the virus are a desperate need. The SARS-CoV-2 spike (S) protein is an important target protein as it mediates the entry of the virus inside the host cells, which is initiated by the binding of the receptor-binding domain (RBD) to its cognate receptor, angiotensin-converting enzyme 2 (ACE-2). Herein, the inhibition potential of several naturally occurring coumarins was investigated against the spike proteins of SARS-CoV-2 variants using computational approaches. Molecular docking studies revealed 26 coumarins with better binding energies than the reference ligands, molnupiravir and ceftazidime, against the S-RBD of the omicron variant. The top 10 best-docked coumarins were further analyzed to understand their binding interactions against the spike proteins of other variants (wild-type, Alpha, Beta, Gamma, and Delta), and these studies also demonstrated decent binding energies. Physicochemical, QSAR, and pharmacokinetics analyses of the coumarins revealed wedelolactone as the best inhibitor of the spike protein with ideal Lipinski's drug-likeness and optimal ADMET properties. Furthermore, coarse-grained molecular dynamics (MD) simulation studies of spike protein-wedelolactone complexes validated the stable binding of wedelolactone in the respective binding pockets. As an outcome, wedelolactone could be utilized to develop a potent drug candidate against COVID-19 by blocking the viral entry into the host cell. [ABSTRACT FROM AUTHOR]