Status of advanced respiratory syncytial virus antiviral therapeutics 2025.

Respiratory syncytial virus (RSV) causes major morbidity and mortality in vulnerable populations. In infants, RSV infection is a leading cause of hospitalization and can result to severe respiratory complications marked by bronchiolitis and viral pneumonia. Currently, prophylaxis exists in the form of three licensed vaccines, all approved for adults aged >65 years or pregnant women, but no vaccination is available specifically for infants. Prophylactic monoclonal antibody treatments, palivizumab and nirsevimab, are recommended in some instances for newborns, but treatment cost and need for intravenous administration limit universal accessibility. The only antiviral approved for the RSV indication, ribavirin, is no longer recommended for clinical use, creating an urgent need for a novel generation of effective therapeutics. Extensive anti-RSV drug discovery efforts have long been dominated by viral entry inhibitors that emerged as pharmacodominant in automated drug discovery campaigns, yet more recently developed candidates have expanded the target range to the viral polymerase complex and nucleoprotein. Focusing on advanced therapeutic candidates and investigational drugs that have entered clinical trials, this review will discuss challenges in RSV drug development in perspective of recent breakthroughs in RSV prophylaxis, assess the current stage of RSV therapeutic candidates, and identify key requirements for future improved RSV disease management.