Publications

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) remains a significant global health threat, necessitating the development of effective antiviral therapeutics. Targeting the heptad repeat 2 (HR2) domain of the MERS-CoV spike protein offers a promising strategy to inhibit viral fusion and entry into host cells. This study investigates a panel of antiviral peptides (AVPs), focusing on Griffithsin, Brevinin-2, and CCL20, to evaluate their potential as fusion inhibitors against the HR2 domain. Employing comprehensive computational approaches, including molecular docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy calculations, we characterized the peptide-protein interactions and stability of these AVPs in complex with HR2. Our results demonstrate that Griffithsin, Brevinin-2, and CCL20 exhibit stronger binding affinities (- 213.69, -168.83, and -165.17 kcal/mol, respectively) compared to the standard inhibitor Peptide-6 (- 49.73 kcal/mol). MD simulations reveal stable complexes and indicate disruption of critical hydrogen bonds in the Ile1255-Gln1271 region of HR2, essential for six-helix bundle formation and viral fusion. Physicochemical analyses further suggest favorable stability, half-life, and low hemolytic potential, supporting their suitability as therapeutic candidates. These findings align with prior studies highlighting the broad-spectrum antiviral activity of Griffithsin and validate the therapeutic promise of Brevinin-2 and CCL20. While this computational investigation lays the groundwork, further in vitro and in vivo validation and optimization of pharmacokinetics and delivery are necessary for clinical development. This study advances the rational design of peptide-based fusion inhibitors targeting MERS-CoV and provides valuable insights into antiviral strategies against emerging coronaviruses.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by cholinergic dysfunction, amyloid-β aggregation, mitochondrial stress, and aberrant kinase activity. Carotenoids, naturally occurring pigments with antioxidant and neuroprotective properties, have emerged as promising candidates for AD intervention. In this study, we performed a systematic stepwise computational screening of a large carotenoid library (n = 1191) to identify multitarget candidates against AD-related proteins. The workflow consisted of predefined ADMET filtering (oral absorption > 90%, Caco-2 > 0.9, logBB > -1, and absence of major CYP inhibition and toxicity alerts), reducing the dataset to 61 compounds, followed by multi-target molecular docking against AChE, BChE, BACE-1, MAO-B, and GSK3-β. Compounds were ranked using an aggregated mean docking score across all five targets, and the top-performing candidate was subjected to detailed mechanistic analyses. Hopkinsiaxanthin emerged as the highest-ranked multitarget carotenoid and was further evaluated using frontier molecular orbital (FMO) analysis, pharmacophore modeling, 100 ns molecular dynamics (MD) simulations, MM/PBSA binding free energy calculations, and per-residue decomposition. Docking predicted favorable estimated binding affinities toward all targets. MD simulations confirmed stable receptor-ligand complexes with low RMSD values (0.278-0.285 nm). MM/PBSA analysis indicated favorable binding free energies, particularly for GSK3-β (-22.73 kcal/mol) and AChE (-21.50 kcal/mol). Per-residue decomposition identified key hotspot residues driving stabilization. Overall, this structured computational framework identifies Hopkinsiaxanthin as a promising multitarget scaffold and supports its prioritization for experimental validation in AD models.