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- The convergence of precision medicine strategies, CRISPR gene editing technologies, and artificial intelligence (AI) is causing a revolutionary change in the pharmaceutical industry in recent times. Latest trends and future directions of these integrated technologies in pharmaceutical science and molecular biology are presented in the present exhaustive review. With more than 250 gene-editing clinical trials being tracked internationally as of February 2025, the recent clinical successes point toward the therapeutic potency of CRISPR-based therapeutics. In parallel, AI-based drug discovery platforms are recording fantastic hit rates; compared to conventional industry benchmarks, AI-emerging drugs reflect 80-90% Phase I trial success rates. Therapeutic development paradigms are being transformed by the intersection of machine learning algorithms, multi-omics technologies, and precision medicine paradigms. The review provides insights into the revolutionary potential of these converging approaches in addressing unmet medical requirements and optimizing therapeutic benefits through syntheses of existing evidence from clinical trials, regulatory matters, and technological innovations.
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- Background: Dental caries arise from polymicrobial biofilms and require interventions that address both local virulence and systemic burden. Methods: A curated set of 124 neem-derived phytochemicals was screened against Streptococcus mutans glucansucrase (3AIC) and Staphylococcus aureus DNA gyrase B (3U2D) using harmonized AutoDock Vina parameters. Ligand standardization and receptor preparation followed conventional protocols. Results: The most favorable docking scores reached −10.7 kcal·mol−1 for 3AIC and −8.9 kcal·mol−1 for 3U2D. Redocking produced pose RMSD values of 1.52 Å (3AIC) and 0.96 Å (3U2D). Per-receptor ADMET profiles for the six top-ranked compounds indicated median logP values of 4.93 (3AIC) and 4.52 (3U2D), median TPSA values of 80.3 and 62.9 Å2, median rotatable bonds of 2.5 and 1.0, and median QED values of 0.41 and 0.76, respectively. Conclusions: An integrated, dual-target screen prioritized neem constituents with plausible local anti-cariogenic activity and physicochemical features compatible with systemic disposition. These in silico findings motivate targeted experimental validation.
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- Malaria remains a significant global health problem; with the potential for developing resistance to conventional antimalarials justifying novel therapeutic approaches. This study investigates the potential of microalgal metabolites as dual-inhibitors of Plasmodium falciparum glutathione S-transferase (PfGST) and apical membrane antigen 1 (AMA1); two of the most important proteins in parasite survival and host cell invasion. By high-throughput molecular docking simulations; we studied binding energy distributions; conformational characteristics by principal component analysis; pharmacophoric and pharmacokinetic research with structure-activity relationships of its inhibitors. Our findings indicate various patterns of interactions: PfGST exhibits a unimodal distribution of binding energy with a maximum at -7.2 kcal/mol; whereas AMA1 exhibits a bimodal distribution with minimum at -6.8 and − 8.3 kcal/mol; suggesting various mechanisms of binding. Specifically; platencin was among the most potent dual-inhibitors with binding energies of -7.30 kcal/mol to PfGST and − 8.20 kcal/mol to AMA1. Pharmacophoric characteristics were found to be the hydrogen-bond acceptors; hydrophobic centers; and aromatic rings as determinants of dual-target activity; the optimal dual-target inhibitory potential occurring with compounds of balanced physicochemical properties. High-resolution molecular interaction mapping validated that while the two targets identify overlapping classes of interactions with the metabolites; PfGST interaction is dominated by hydrophobic contacts and AMA1 exploits higher electrostatic complementarity and hydrogen-bonding networks. ADMET profiling also revealed favorable drug-likeness in dual-inhibitory compounds of intermediate molecular size (420–500 Da) and moderate lipophilicity (LogP 3–6). This study provides a structural basis for rationale design of antimalarial compounds from microalgal metabolites. Our findings confirm the conformational selection hypothesis; in which these compounds selectively bind to and stabilize protein conformations that inhibit parasite function; possibly circumventing known resistance mechanisms.
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- Background The increasing global incidence of breast cancer calls for the identification of new therapeutic targets and the assessment of possible neem-derived inhibitors by means of computational modeling and integrated genomic research. Methods Originally looking at 59,424 genes throughout 42 samples, we investigated gene expression data from The Cancer Genome Atlas—Breast Cancer (TCGA-BRCA) dataset. We chose 286 genes for thorough investigation following strict screening for consistent expression. R’s limma package was used in differential expression analysis. The leading candidate’s protein modeling was done with Swiss-ADME and Discovery Studio. Molecular docking studies, including 132 neem compounds, were conducted utilizing AutoDock Vina. Results Among the 286 examined, mitochondrially encoded cytochrome C oxidase III (MT—CO3) turned out to be the most greatly overexpressed gene, showing consistent elevation across all breast cancer samples. Protein modeling revealed a substantial hydrophobic pocket (volume: 627.3 Å3) inside the structure of MT—CO3. Docking investigations showed five interesting neem-derived inhibitors: 7-benzoylnimbocinol, nimolicinol, melianodiol, isonimocinolide, and stigmasterol. Strong binding affinities ranging from −9.2 to −11.5 kcal/mol and diverse interactions with MT—CO3, mostly involving the residues Phe214, Arg221, and Trp58, these molecules displayed. With hydrophobic interactions dominant across all chemicals, fragment contribution analysis revealed that scaffold percentage greatly influences binding effectiveness. Stigmasterol revealed greater drug-likeness (QED = 0.79) despite minimal interaction variety, while 7-benzoylnimbocinol presented the best-balanced physicochemical profile. Conclusion Connecting traditional medicine with current genomics and computational biology, this work proposes a methodology for structure-guided drug design and development using neem-derived chemicals and finds MT—CO3 as a potential therapeutic target for breast cancer.
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- Alzheimer’s disease (AD) is characterized by the accumulation of amyloid beta plaques and neurofibrillary tangles composed of hyperphosphorylated tau protein. This study computationally investigated natural neem compounds (limonoids) and gut microbiome metabolites for their inhibitory potential against key AD targets. Molecular docking analyses were performed on approximately 200 neem phytochemicals and 9 microbial metabolites against betasecretase 1 (BACE1), gingipain cysteine protease, and tau oligomerization receptors using AutoDock. BBB permeability was computationally evaluated using six molecular descriptors: molecular weight, LogP, hydrogen bond acceptors/ donors, polar surface area, and rotatable bonds, categorizing compounds as highly or poorly BBB permeable based on established predictive criteria. The results revealed superior binding affinities of limonoids, notably Rutin (− 9.642 kcal/ mol), 7-benzoylnimbocinol (−9.706 kcal/mol), and tirucallol (−9.488 kcal/mol) against BACE1, gingipain protease, and tau oligomerization receptors, respectively. These compounds exhibited key interactions through hydrogen bonding with Gly34, Asn233 (rutin-BACE1), Lys311, and Asn363 (7-benzoylnimbocinol-gingipain) and hydrophobic interactions with Ile40 and Ile48 (tirucallol-tau). While these limonoids demonstrated binding affinities exceeding melatonin by >30%, their BBB permeability profiles necessitate sophisticated delivery strategies. Among gut microbiome metabolites, melatonin showed consistent binding across all targets (−7.079 to −8.452 kcal/mol). These findings establish limonoids’ superiority over gut microbiome metabolites and highlight their therapeutic potential as multi-target inhibitors in AD pathology, warranting investment in nanocarrier systems for optimizing BBB penetration.
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