Advances in respiratory syncytial virus therapeutics: A comprehensive review of small-molecule inhibitors, monoclonal antibodies, and vaccines.

Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections in infants, elderly individuals, and immunocompromised individuals, and poses a substantial global health burden. Despite the clinical use of ribavirin and the monoclonal antibody palivizumab, their limitations in efficacy, safety, and cost necessitate the development of novel anti-RSV agents. This comprehensive review summarizes the progress in RSV therapeutics over the past decade (2015-2025), focusing on three major categories: small-molecule inhibitors, monoclonal antibodies, and vaccines. Small-molecule inhibitors, including fusion inhibitors targeting the F protein, nucleoside and non-nucleoside polymerase inhibitors, and nucleoprotein inhibitors, are discussed in detail. The review also covers approved and emerging monoclonal antibodies and vaccines, highlighting their mechanisms, clinical status, and limitations. Key challenges such as drug resistance, target specificity, and patient heterogeneity are addressed, and future directions-including structure-based drug design, host-targeted therapies, drug repurposing, and combination strategies-are proposed. This review aims to provide medicinal chemists with a structured update on RSV drug discovery and to accelerate the development of effective antiviral strategies.