Ebola virus disease remains one of the most serious viral infections with no approved small-molecule treatments. The Ebola virus glycoprotein (EBOV-GP), which enables the virus’s entry to host cells, is a promising target for drug discovery. In this study, a multistage computer-aided drug discovery approach was used to identify new specific EBOV-GP inhibitors. A reliable QSAR model was built using 55 terpenoid derivatives. This model was able to predict the activity of newly designed compounds with good accuracy and validated statistical metrics ($R_{tr}^2$= 0.70; $R_{ext}^2$ = 0.73). It was subsequently applied to screen over 15,500 newly generated compounds from three lead molecules by fragment-based design tools. Predicted activity, binding affinity toward EBOV-GP, and good ADMET drug-like properties prioritized the eleven most promising hits. Through 150 ns molecular dynamics simulations, these compounds remained stable in the EBOV-GP binding site. Further binding free energy analysis (MM/PBSA) showed strong binding affinities, especially for the compounds L-60, L-832, M-1618, and L-1366. This study showed how combining QSAR, fragment-based design, docking, ADMET, and molecular dynamics could help in identifying potent and safe small molecules against the EBOV-GP. The top compounds are ready for further experimental and in vitro biological testing.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by excessive extracellular matrix remodeling and limited therapeutic options. Matrix metalloproteinase-2 is involved in extracellular matrix degradation and tissue remodeling, making it a relevant target for antifibrotic drug discovery. In this study, an MMP2-focused ligand-based pharmacophore model was developed and was applied to screen a curated FDA-approved drug library, leading to the identification of 83 pharmacophore-matching compounds. These compounds were subsequently prioritized through molecular docking against the catalytic site of MMP2, and the five best candidates were further evaluated by molecular dynamics (MD) simulations. Because of the biological relevance of MMP3 in pulmonary fibrosis, these five selected compounds were also profiled against MMP3 as a secondary target. Among them, Regorafenib (S1178) and Capmatinib (S2788) showed the most favorable cross-target profiles and were further supported by MD analysis. From these findings, S1178 and S2788 were proposed as promising MMP2-prioritized compounds with potential MMP3 cross-activity, warranting further experimental validation as candidate antifibrotic MMP modulators.

Harmful algal blooms pose a persistent threat to the integrity of freshwater ecosystems and public health. However, there are no selective chemical control agents available to suppress cyanobacterial growth without damaging beneficial phytoplankton. In this study, ten structurally diverse monoterpenes were assessed in vitro for their differential activity against the potent toxin-producing cyanobacterium Microcystis aeruginosa and the ecologically valuable microalga Chlorella sorokiniana using disc diffusion (DDM) and minimum inhibitory concentration (MIC) assays. Inhibition zones against M. aeruginosa ranged from 6.9 to 43.6 mm, with thymol recording the largest zone (43.6 mm). MIC values ranged from 0.25 to >1 mg/mL for both organisms, and selectivity indices identified camphor and carvone as the most cyanobacterium-preferential compounds, while carene and α-pinene showed the inverse selectivity pattern. Molecular docking against six AlphaFold2-predicted target proteins, photosynthetic complexes, Adenosine Triphosphate (ATP) synthase subunits, and superoxide dismutase (SOD) from both organisms, revealed binding affinities between −3.9 and −6.2 kcal/mol. Phenolic monoterpenes consistently engaged active-site glutamate and aspartate residues via hydrogen bonds and Pi–Anion interactions, most strikingly in the M. aeruginosa ATP synthase, whereas the M. aeruginosa SOD represented the least amenable target for all compounds. Computational ADMET profiling confirmed favorable pharmacokinetic properties and low predicted toxicity for the full panel.