Single-Dose Anti-Influenza Therapies: Current Progress and Future Perspectives

Influenza remains a major global health challenge, with seasonal epidemics causing 3-5 million severe cases and 290,000-650,000 deaths annually. Existing antiviral agents, while clinically useful, face limitations including narrow spectrum, drug resistance, and multi-dose regimens that compromise patient adherence. Single-dose anti-influenza therapy has emerged as a promising strategy to address these challenges by simplifying treatment and improving compliance. This review systematically summarizes recent advances in three classes of single-dose agents: polymerase acidic (PA) endonuclease inhibitors (baloxavir marboxil, suraxavir marboxil, sebaloxavir marboxil, pixavir marboxil, ADC189), neuraminidase inhibitors (e.g., the long-acting Fc conjugate CD388), and polyclonal antibodies (SAB-176). We discuss their mechanisms of action, clinical trial outcomes, and resistance profiles. The comparative analysis reveals that these three classes are not competitive alternatives but rather address distinct clinical needs: PA inhibitors provide convenient acute-phase oral therapy with rapid symptom relief but face I38T/M resistance mutations; CD388 offers extended protection suitable for seasonal prophylaxis in high-risk populations; and SAB-176 represents a passive immunization strategy for immunocompromised patients. Key challenges remain, particularly the I38T/M resistance shared across PA inhibitors and the need for head-to-head clinical comparisons. Together, these developments mark significant progress toward effective, convenient, and resistance-aware influenza management.