SRM-2025: A Theoretically Derived Macrocyclic Polyketide--Nitroimidazole Hybrid Predicted to Exhibit Pan-Filaricidal Activity Across All Life Stages via Dual Wolbachia-Dependent and Nematode-Specific Metabolic Ablation

This study introduces a de novo computational framework for SRM-2025 (proposed trade name: FilariCida™; C32H41N5O7), a novel antifilarial compound candidate predicted to exhibit potent activity against all developmental stages of Onchocerca volvulus and Wuchereria bancrofti, with minimal predicted cytotoxicity to human cells. The design integrates (i) predicted covalent inhibition of Wolbachia ferrochelatase (HemH) and (ii) predicted competitive inhibition of nematode-specific N-myristoyltransferase (NMT). Evaluation encompassed a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model with Bayesian uncertainty quantification and global sensitivity analysis (Sobol' indices), in silico ADMET profiling using SwissADME, and molecular dynamics (MD) simulations to assess protein-ligand complex stability. Virtual toxicity screening addressed nitroimidazole-related concerns. All workflows are reproducible via open-source Python code utilizing SciPy and NumPy. References are drawn solely from peer-reviewed publications (2012--2024) and WHO reports.