BPS2026 – Nucleoprotin mutations linked to pediatric respiratory virus infection: A computational study

Respiratory syncytial virus (RSV) remains a significant global health concern, particularly affecting vulnerable pediatric populations. Aberrations in protein folding and structural integrity are known to contribute to various human diseases. This study investigates the structural and functional consequences of nine specific mutations within the RSV nucleoprotein (N): F300A, F320A, K107Q, L272A, R234A, R259A, T54N, Y288A, and Y353A. Through comprehensive bioinformatics analyses, mutant N protein models were generated, evaluated, and compared to the wild-type structure. Molecular dynamics simulations extending beyond 100 nanoseconds were conducted to assess conformational behavior using RMSD, RMSF, radius of gyration, and solvent accessibility metrics. Additionally, predictive tools including PolyPhen-2, MutPred2, DUET, mCSM, SDM, and MAESTRO were employed to evaluate the impact of these mutations on protein stability. The findings reveal distinct structural disruptions associated with each variant, offering insights into their potential roles in RSV pathogenesis. This work highlights the nucleoprotein as a promising therapeutic target and contributes to the development of precision strategies for managing RSV-related respiratory infections in children.