Chronic inflammation contributes to the pathogenesis of many degenerative diseases. Long-term use of conventional anti-inflammatory drugs may be associated with serious adverse effects, prompting the search for new natural candidates. Begonia medicinalis is a plant endemic to Central Sulawesi that is traditionally used to treat fever and joint pain, but its phytochemical profile and molecular mechanisms underlying its potential anti-inflammatory activity have not been scientifically reported. The aim of this study was to identify the secondary metabolite profile of the ethanol extract of B. medicinalis leaves and to assess its molecular interactions with pivotal pro-inflammatory targets, namely cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), using a computational approach. The study combined a laboratory-based phytochemical analysis with in silico analyses, including structure-activity relationship (SAR), absorption, distribution, metabolism, and excretion (ADME), toxicity prediction, molecular docking, and molecular dynamics simulations. B. medicinalis leaves were extracted by maceration using absolute ethanol, and the metabolite profiles were analyzed using gas chromatography-mass spectrometry (GC-MS). Biological activity prediction was performed using PASS Online, pharmacokinetic profiling using SwissADME, toxicity evaluation using ProTox 3.0, and protein-protein interaction analysis using STRING v12.0. Molecular docking was performed using PyRx with AutoDock Vina and visualized using BIOVIA Discovery Studio 2025. GC-MS analysis identified 21 compounds, including palmitic acid, dihomo-γ-linolenic acid, and stigmasterol, which showed predicted anti-inflammatory potential, favorable safety profiles, and acceptable drug-likeness characteristics. Among these compounds, stigmasterol showed favorable predicted binding affinities toward COX-2, iNOS, TNF-α, and IL-1β, while molecular dynamics simulations supported the stability of the resulting complexes over 100 ns. These computational findings suggest that B. medicinalis contains diverse bioactive compounds with potential anti-inflammatory properties. Stigmasterol emerged as the most promising lead candidate against the predicted anti-inflammatory targets, providing a theoretical molecular foundation for the future exploration of B. medicinalis therapeutic potential.
Ni KD. Permatasari, Sri Wahyuningsih, Felisitas M. Podhi et al.· Narra X· 0 citations
Triple-negative breast cancer (TNBC) remains a major therapeutic challenge because of its aggressive behavior, molecular heterogeneity, and limited subtype-specific targets. This study used an integrated immunoinformatics workflow to design a recombinant tumor-associated antigen-derived multi-epitope vaccine based on MMP1, CXorf61/CT83, and COL11A1, prioritized according to their tumor-to-normal transcript-expression ratios. Candidate cytotoxic T-lymphocyte, helper T-lymphocyte, and linear B-cell epitopes were screened for predicted HLA binding, antigenicity, allergenicity, toxicity, and IFN-γ-induction potential. The selected epitopes were assembled with PADRE, a MyD88-derived exploratory immunomodulatory domain, class-specific linkers, and a C-terminal histidine tag to generate a 621-amino-acid construct. Combined HLA class I and II analysis predicted 99.36% worldwide population coverage, with 3.14 epitope–HLA hits per individual. The construct was predicted to be antigenic, non-allergenic, soluble, and physicochemically compatible with recombinant production. Structural modeling yielded a ProSA Z-score of −7.43 and 97.45% of residues in favored Ramachandran regions, while disulfide engineering identified ten candidate intramolecular bridges. Docking produced an HDOCK score of −298.65 for the modeled vaccine–TLR4 complex, and flexibility analysis showed an average RMSF of 1.93 Å. Immune simulation predicted Th1-associated cytokine production, T-cell expansion, antibody responses, and memory-cell formation. Codon optimization generated a CAI of 0.95 and a GC content of 53.2%, followed by virtual cloning into pET-28a(+). These findings support the computational feasibility of the proposed vaccine candidate, which requires experimental validation of expression, antigen processing, HLA presentation, immunogenicity, safety, and antitumor activity.
M. R. Afnani, Volta Kellik Setiawan, Anwar Rovik· Natural and Life Sciences Co...· 0 citations
Influenza A (H5N1) remains a major public health concern due to its high pathogenicity and ongoing viral evolution, underscoring the need for novel antiviral candidates.
In this study, we performed an integrated
in silico
evaluation of organosulfur compounds derived from
Allium ascalonicum
L. (shallot) cultivated in the Tolaki-Mekongga region, Sulawesi, Indonesia, targeting key viral proteins including polymerase (PB2), nucleoprotein (NP), and neuraminidase (NA).
Density functional theory (DFT) analyses were conducted to characterize the electronic properties of the compounds, while PASS prediction indicated moderate potential antiviral activity for Propanethiol and Dipropyl disulfide. Pharmacokinetic profiling suggested acceptable ADMET properties for several candidates. Molecular docking revealed favorable binding conformations across all targets, with γ-glutamyl-S-propenylcysteine exhibiting the most favorable binding energies among the evaluated organosulfur compounds (PB2: -4.9 kcal/mol; NP: -5.8 kcal/mol; NA: -5.2 kcal/mol). These values were comparable to those of oseltamivir and favipiravir for NP and NA, although weaker binding was observed against PB2. Subsequent simulations of molecular dynamics demonstrated stable protein–ligand complexes over 100 ns, further supporting the predicted binding interactions. Consistently, MM-GBSA calculations indicated favorable binding free energies, particularly for γ-glutamyl-S-propenylcysteine (PB2: -30.52 ± 0.29 kcal/mol; NP: -22.76 ± 0.12 kcal/mol; NA: -26.13 ± 0.35 kcal/mol).
Overall, these findings suggest that shallot-derived organosulfur compounds, especially γ-glutamyl-S-propenylcysteine, exhibit potential for interaction with H5N1 viral targets and may warrant further investigation as antiviral candidates. Experimental validation through
in vitro
and
in vivo
studies is required to confirm their biological activity and therapeutic potential.
Rangga Adhi Prastika, Alifaghi Pahlevi Ervianto Putra, Muhammad Alesha Fadhana et al.· Frontiers in Virology· 0 citations
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