Jagathala Mahalingam Sasikumar

Epidermal growth factor receptor (EGFR) mutations drive hepatocellular carcinoma (HCC) progression, and the T790M gatekeeper substitution is the predominant mechanism of acquired resistance to EGFR-targeted therapies. Herein, we present multiscale quantum-classical in silico predictions of Phyllanthus niruri phytochemicals as non-covalent EGFR T790M binders, employing molecular docking, 100 ns molecular dynamics, MM-PBSA/MM-GBSA, per-residue decomposition, PCA/LDA, DFT at B3LYP-D3(BJ)/def2-TZVP, and comparative wild-type EGFR simulations. Five phytochemicals exhibited computationally predicted binding affinities against EGFR T790M exceeding the non-covalent binding component of osimertinib (−25.74 kcal/mol): corilagin (−53.71 ± 5.05 kcal/mol), eriodictyol-7-rhamnopyranoside (−44.35 ± 4.51 kcal/mol), isoquercetin (−44.23 ± 2.92 kcal/mol), rutin (−42.15 ± 4.50 kcal/mol), and kaempferol-4-rhamnoside (−41.68 ± 3.69 kcal/mol). Wild-type EGFR simulations (PDB 1M17) yielded a selectivity index (IS) of 2.76 for corilagin (ΔΔG_bind = +34.22 kcal/mol), indicating T790M-preferential binding. Osimertinib reproduced its clinically established T790M selectivity under identical conditions (IS = 1.43; ΔΔG_bind = +7.74 kcal/mol), providing internal methodological validation. DFT at B3LYP-D3(BJ)/def2-TZVP established the quantum-mechanical basis for corilagin’s electrostatic affinity: its molecular electrostatic potential (MEP) surface minimum (V_s,min = −46.92 kcal/mol) directly predicts the largest MM-PBSA electrostatic term (ΔE_ele = −52.48 kcal/mol), establishing quantum-classical coherence. Supervised PCA/LDA of 7416 MM-PBSA trajectory frames identified solvation energy (ΔG_SOLV) as the primary pharmacological class discriminant, with the first discriminant function (LD1) capturing 93.1% of inter-class binding variance. Collectively, corilagin (hydrolyzable tannin), eriodictyol-7-rhamnopyranoside (flavonoid glycoside), and phyltetralin (lignan) constitute diverse computational leads from P. niruri warranting experimental validation as T790M-directed agents in HCC.

Seaweeds, or macroalgae, are recognized for their medicinal and edible properties and are commonly utilized in the pharmaceutical and food industries. This study aimed to investigate the phytochemical components, antioxidant properties, in vitro antidiabetic effects, and antibacterial activities of Stoechospermum polypodioides, a macroalga from the southern coast of India. The phenolic composition was quantified using the Folin-Ciocalteu assay, while the total flavonoid content was measured using the aluminium chloride method. Antioxidant activity was evaluated through DPPH radical and ABTS cation scavenging assays, total antioxidant capacity (TAC), and ferric reducing ability. Inhibition assays for α-amylase and α-glucosidase were conducted to explore the antidiabetic potential. Antibacterial activity was tested against four bacterial pathogens. The phenolic content of the methanol extract of S. polypodioides was found to be 350 ± 10.14 mg GAE/g, and the flavonoid content was 206.8 ± 7.43 mg QE/g. The methanol extract demonstrated scavenging activity against DPPH and ABTS, with IC50 values of 29.22 µg/ml and 31.20 µg/ml, respectively. An effective reduction of Mo(VI) to Mo(V) was also noted, with an IC50 of 44.2 µg/ml. Additionally, the extract showed strong reducing ability, evidenced by an absorbance of 0.987 ± 0.012 at 700 nm at the highest concentration tested (1000 µg/ml). Furthermore, the methanol extract effectively inhibited α-amylase (IC50 = 21.6 µg/mL) and α-glucosidase (IC50 = 22.6 µg/mL). The S. polypodioides extract also exhibited significant antibacterial activity, particularly against Staphylococcus aureus. Based on these bioactivities, S. polypodioides may be considered a potential source of bioactive agents.

The COVID-19 pandemic exposed critical vulnerabilities in single-target antiviral strategies, highlighting the urgent need for multi-mechanism therapeutic approaches against emerging viral threats. Here, we present an integrated computational framework systematically evaluating natural fatty acids as potential dual ACE2 (Angiotension Converting Enzyme 2)-inflammatory modulators; compounds simultaneously disrupting SARS-CoV-2 viral entry through allosteric ACE2 binding while suppressing host inflammatory cascades; through allosteric binding mechanisms rather than conventional competitive inhibition. Using molecular docking across eight ACE2 regions, 100 ns molecular dynamics simulations, MM/PBSA free energy calculations, and multivariate statistical analysis (PCA/LDA), we computationally assessed nine naturally occurring fatty acids representing saturated, monounsaturated, and polyunsaturated classes. Hierarchical dynamics analysis identified three distinct binding regimes spanning fast (τ < 50 ns) to slow (τ > 150 ns) timescales, with unsaturated fatty acids demonstrating superior binding affinities (ΔG = −6.85 ± 0.27 kcal/mol vs. −6.65 ± 0.25 kcal/mol for saturated analogs, p = 0.002). Arachidonic acid achieved optimal SwissDock affinity (−7.28 kcal/mol), while oleic acid exhibited top-ranked predicted binding affinity within the computational hierarchy (ΔG_bind = −24.12 ± 7.42 kcal/mol), establishing relative prioritization for experimental validation rather than absolute affinity quantification. Energetic decomposition identified van der Waals interactions as primary binding drivers (65–80% contribution), complemented by hydrogen bonds as transient directional anchors. Comprehensive ADMET profiling predicted favorable safety profiles compared to synthetic antivirals, with ω-3 fatty acids showing minimal nephrotoxicity risks while maintaining excellent intestinal absorption (>91%). Multi-platform bioactivity analysis identified convergent anti-inflammatory mechanisms through eicosanoid pathway modulation and kinase inhibition. This computational investigation positions natural fatty acids as promising candidates for experimental validation in next-generation pandemic preparedness strategies, integrating potential therapeutic efficacy with sustainable sourcing. The framework is generalizable to fatty acids from diverse biological origins.

In recent times, attention has been paid to phyto-assisted synthesis of nanoparticles using plant extracts due to its ecofriendly, low cost and easy modes. In our research, silver nanoparticles (AgNPs) were synthesized using methanolic root extract of Verbena officinalis L. The AgNPs were tested for antibacterial activity against Escherichia coli ATCC-O157 H: 7 and Staphylococcus aureus ATCC-25923 using the disc diffusion method and minimum inhibitory concentration (MIC) determination. The AgNPs formation was initially observed by the color change and further verified using UV-Vis spectrophotometer, Fourier Transform Infra-red (FT-IR) and X- Ray crystallography (XRD). The color change from yellow to brown in the reaction mixture was an indication for the synthesis of AgNPs. Further confirmation was established 434 nm in UV-Vis spectroscopy. The FTIR analysis displayed bands analogous to functional groups of plant’s phytochemicals that were accountable for reducing and capping of AgNPs. The AgNPs analysis by XRD validated the crystallinity of AgNPs at 2? angles of 38.000, 44.160, 64.400, and 77.330 harmonizing to planes at (111), (200), (220), and (311), respectively and established their average size (22.67 nm). The AgNPs exhibited strong antibacterial potential against the tested pathogenic bacteria. The AgNPs exhibited significantly (p<0.001) better antibacterial effect against S. aureus than E. coli. The smallest MIC of 10.42 µg/mL was observed against S. aureus. These outcomes apparently demonstrated the efficacy of the components of the V. officinalis root extract in the significant enrichment of the toxicity of the AgNPs against the bacterial pathogens.In recent times, attention has been paid to the green synthesis of nanoparticles using plant extracts due to their eco-friendly, low-cost and easy modes. In the present research, silver nanoparticles (AgNPs) were synthesized using methanolic root extract of Verbena officinalis L. The AgNPs were tested for antibacterial activity against Escherichia coli ATCC-O157 H: 7 and Staphylococcus aureus ATCC-25923 using the disc diffusion method and minimum inhibitory concentration (MIC) determination. The AgNPs formation was initially observed by the color change and further verified using UV-Vis spectrophotometer, Fourier Transform Infra-red (FT-IR) and X-Ray crystallography (XRD). The color change from yellow to brown in the reaction mixture was an indication of the synthesis of AgNPs. Further confirmation was established at 434 nm in UV-Vis spectroscopy. The FTIR analysis displayed bands analogous to functional groups of the plant’s phytochemicals that were accountable for reducing and capping of AgNPs. The AgNPs analysis by XRD validated the crystallinity of AgNPs at 2? angles of 38.00°, 44.16°, 64.40° and 77.33° harmonizing to planes at (111), (200), (220) and (311), respectively and established their average size (22.67 nm). The AgNPs exhibited strong antibacterial potential against the tested pathogenic bacteria. The AgNPs exhibited significantly (p<0.001) better antibacterial effect against S. aureus than E. coli. The smallest MIC of 10.42 ?g/mL was observed against S. aureus. These outcomes demonstrated the efficacy of components of the V. officinalis root extract in the significant enrichment of the toxicity of the AgNPs against the bacterial pathogens.

This study aimed to isolate a fungal strain capable of producing acidophilic and thermostable polygalacturonase. In this study, the fungal isolate was isolated from decaying tomatoes. Based on the colony characteristics, microscopic and morphological observations, the isolated fungal pathogen has been identified as Aspergillus niger. The isolated fungus was used in solid-state fermentation to produce an acidic polygalacturonase enzyme. The enzyme was then purified using ammonium sulphate precipitation and column chromatography, and its activity was assayed by measuring the releasing sugar group from citrus pectin using a 3, 5-dinitrosalicylic acid (DNSA) reagent assay. The crude extract obtained from solid-state fermentation had an activity of 94.6 U/mL. Ammonium sulphate precipitation increased the enzyme's specific activity from 6.89 U/mg to 12.42 U/mg. Sephadex G-200 was used to purify the enzyme 3.58 times, and its specific activity was determined to be 24.66 U/mg. The Sephacryl S-100 column achieved a final fold purification of 9.93 times and a specific activity of 68.41 U/mg. The purified enzyme performed best when polygalacturonic acid was used as a substrate. The enzyme's optimum temperature and pH were 55°C and 5, respectively. CaCl2 was found to be the best chelating ion for the enzyme. This enzyme is recommended for use in a variety of industrial applications as the enzyme was found to be stable at acidic pH and high temperature.

Floristic composition, population structure, and regeneration status of woody species of Dabal forest found in East Hararghe zone of Oromia Regional State, Ethiopia, were studied. Vegetation data were obtained from 52 main plots of 20 × 20 m for mature woody species and 5 subplots of 5 × 5 m for seedlings and saplings. Density and dbh of each live woody plant species found in each sample plot were recorded. Frequency, basal area, importance value, and Shannon–Wiener diversity indices were also computed. Totally 59 woody plant species distributed in 33 families were documented. Of these, 45.80, 44.10, and 5.08% were shrubs, trees, and lianas, respectively. Species diversity and evenness indices were 3.56 and 0.87, respectively. Stem count of all woody species was 3379 stems ha⁻¹. Out of this, 44.6, 30.8, and 24.59% were seedlings (dbh 10 cm) individuals, respectively. Total basal area of all individuals with dbh ≥3.5 cm was 29.88 m² ha⁻¹. Juniperus procera, Cupressus lusitanica, Eucalyptus globulus, Afrocarpus falcatus, Eucalyptus camaldulensis, Myrsine africana, Maytenus undata, Hagenia abyssinica, Ekebergia capensis, and Cordia africana were species with top ten IVI. Most of these species were top densest, dominant, and frequent. Analysis of population structure based on pooled densities of all species in each dbh class showed that density of seedling > sapling > mature individuals, signifying healthy population structure with good natural regeneration potential. On individual basis, however, 35.6 and 8.5% of species showed fair and poor regeneration statuses, respectively, that deserve attention for conservation.

Background: Phyto-fabrication of nanoparticles has gained attention in recent times owing to its simple mode, cost-effective and eco-friendly nature. Objective: Hence, the present study aimed to synthesize cobalt oxide nanoparticles from methanol extracts of Ocimum gratissimum flower and leaf and to evaluate their antimicrobial action towards pathogenic bacteria and fungi. Methods: Phyto-fabrication of Cobalt nanoparticles (CoONPs) was achieved using cobalt chloride hydrate solution as a precursor. Characterization of fabricated CoONPs was performed using Ultra Violet-Visible spectrometry (UV-Vis), X-ray diffractometer (XRD), and Fourier Transform-Infrared spectroscopy (FTIR). The antimicrobial property was tested against two bacteria (Staphylococcus aureus and Escherichia coli) and two fungi (Cryptococcus albidus and Candida globasa) by agar disc diffusion technique and by measurement of Minimum Inhibitory Concentration (MIC). Results: Initial confirmation of CoONPs synthesis was observed by the colour change from light pink to reddish pink. Further, the UV-Vis spectrophotometry validated the CoONPs synthesis with a peak at 509 nm. The XRD authenticated the crystal nature of CoONPs synthesized using flower extract at 2θ angles with an average size of 54.9 nm and CoONPs fabricated using leaf extract at 2θ angles with an average size of 55.02 nm. The FTIR spectroscopy confirmed the functional groups present in plant extracts, which are believed to reduce and stabilize CoONPs. The findings of antibacterial activity showed that CoONPs synthesized using leaf showed a higher inhibition zone against E. coli (20.00 ± 2.00 mm) than S. aureus. Relating to fungi, the CoONPs fabricated using flower extract displayed significantly the highest activity against C. albidus (28.67±0.57 mm) and C. globasa (25.0 ± 0.00 mm). The lowest MIC was observed against S. aureus (MIC 7.5 µg/ml). For fungi, the smallest MIC was found against C. albidus (MIC 2.5 μg/ml). Conclusion: The current research established the efficacy of the phytochemical constituents of leaf and flower extracts of O. gratissimum for the enhancement of the effectiveness of CoONPs against both the tested bacteria and fungi.

Sesbania sesban (L.) Merr. (Fabaceae) is used in ethnomedicine as a remedy for various ailments. The major objective of this review is to discuss the information on traditional medicinal uses, secondary metabolites composition and bioactive studies on S. sesban. The outcome of the literature survey showed that S. sesban is known to contain flavonols, glycosides, proteins, tannins, triterpenoids, saponins, sterols and steroids. Pharmacological investigations based on in vitro and in vivo studies of S. sesban revealed that it possessed antimicrobial, antioxidant, larvicidal, cytotoxic, anti-inflammatory, antinociceptive, anthelmintic, antidiabetic, antifertility, molluscicidal and spermicidal activities.