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.

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.

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, R_g, 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.

Background: Falconeria insignis Royle, a medicinal plant of the Euphorbiaceae family, has been extensively used in Nepal for bacteria-infected wounds, despite the lack of empirical evidence supporting its efficacy. Objectives: This study aims to evaluate the phytopharmaceutical potential of F. insignis leaves and stems in combating oxidative stress and bacterial infections. Methods: Phytoconstituents were characterized using the LC-MS technique. The antioxidant activity was evaluated through DPPH, nitric oxide, hydroxyl radical, and FRAP assays. Furthermore, antibacterial activity was assessed via in vitro disc diffusion and broth dilution assays, along with in silico molecular docking and ADME-toxicity studies. Results: The phenolic compounds identified include gallic acid, chlorogenic acid, and quercetin. Methanolic leaf extract exhibited significant DPPH radical scavenging activity, with an IC ₅₀ of 5.272 ± 0.5 µg/ml, comparable to that of standard ascorbic acid (IC ₅₀ of 4.05 ± 0.3 µg/ml). Additionally, it also demonstrated a pronounced dose-dependent capacity to scavenge nitric oxide, hydroxyl radicals, and reduce ferric ions. Methanolic leaf and ethyl acetate stem extracts showed promising antibacterial activity against Staphylococcus aureus, with a zone of inhibition (ZOI) ranging from 17 to 24 mm and a minimum inhibitory concentration (MIC) of 15.625 µg/ml. In contrast, standard antibiotic meropenem exhibited a ZOI of 24 ± 1.6 mm and MIC of 1.5625 µg/ml. All identified phytoconstituents displayed strong interactions with the catalytic residues SER 403, LYS 406, SER 462, ASN 464, and THR 600 of the penicillin-binding protein, with binding energies of −6.1 to −7.1 kcal/mol, rivaling meropenem (−7.4 kcal/mol). Furthermore, these compounds were forecasted to be safe in terms of hepatotoxicity, with minimal risks of nephrotoxicity. Conclusion: Our findings establish F. insignis as a promising antioxidant and antibacterial crude drug and recommend further cell line and in vivo validations, along with isolation of antibacterial lead compounds.

Aldose reductase has received extensive research as a key enzyme in the development of long-term problems linked to diabetes mellitus. Overexpression of this enzyme or with exceeded glucose concentration in the blood increases sorbitol on the retina leading to retinopathy, which is the adverse effect of type II diabetes. Approximately 100 million people are suffering from diabetic retinopathy globally. This research is focused on studying the total phenolic content (TPC), total flavonoid content (TFC), antioxidant potential, and aldose reductase inhibiting properties of selected medicinal plants such as Anacyclus pyrethrum, Bergenia ciliata, Rhododendron arboreum, and Swertia chirayita. In addition, ADMET analysis and molecular docking of seven previously identified compounds from the chosen medicinal plants were carried out against human aldose reductase (PDB ID: 4JIR). The ethanol extract of S. chirayita exhibited the highest TPC (4.63±0.16mg GAE/g) and TFC (0.90±0.06mg QE/g). Analysis of 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based antioxidant assay showed that IC₅₀ of the ethanolic extract of B. cilata and R. arboreum showed a significant antioxidant activity with IC₅₀ value of 0.05mg/mL. The percentage inhibition of AR by extract of B. ciliata (94.74±0.01) was higher than other plant extracts. A molecular docking study showed that morin isolated from B. ciliata showed a good binding interaction with AR. This study showed that the extracts of A. pyrethrum, B. ciliata, and R. arboreum could be potential sources of inhibitors against AR to treat retinopathy.

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.