Repurposing antiviral drugs targeting RNA viruses: A focus on the fusion protein of human metapneumovirus.

objectiveHuman metapneumovirus (HMPV) is a clinically important respiratory pathogen causing severe lower respiratory tract infections, particularly in infants, elderly individuals, and immunocompromised patients. Despite its substantial disease burden and global circulation, no HMPV-specific antiviral therapy has been approved to date. This unmet clinical need underscores the importance of identifying rapidly translatable therapeutic strategies. The present study aimed to identify potential inhibitors of the HMPV fusion (F) protein through a structure-based drug repurposing approach, leveraging the advantages of existing safety and pharmacokinetic profiles of approved antivirals.

methodsThirteen antiviral agents predicted to interact with the HMPV F protein were selected from the DrugBank database. Comprehensive in silico molecular docking analyses were conducted to evaluate ligand-protein interactions, with Ribavirin used as a reference compound and positive control. Binding affinity values were quantitatively compared, using the Ribavirin binding energy (-6.2 kcal/mol) as a benchmark for relative performance.

resultsThe docking analyses revealed that multiple approved antiviral agents-namely Ledipasvir, Velpatasvir, Paritaprevir, Elbasvir, Pibrentasvir, Glecaprevir, Voxilaprevir, Ombitasvir, Grazoprevir, Dasabuvir, and Sofosbuvir-exhibited significantly higher binding affinities to the HMPV F protein than Ribavirin. These findings highlight the unexpected and mechanistically relevant interaction potential of hepatitis C virus-targeting antivirals with the HMPV fusion machinery, suggesting a novel avenue for therapeutic intervention.

conclusionThis study provides compelling in silico evidence that drug repurposing of clinically approved antiviral agents may accelerate the development of effective HMPV-specific therapies. By targeting the highly conserved and functionally critical HMPV F protein, the identified candidate compounds offer strong translational potential and justify prioritization for experimental validation and preclinical investigation. Collectively, these results contribute to filling a critical therapeutic gap and support drug repurposing as a viable and time-efficient strategy to address emerging and neglected viral respiratory infections.