Recent Advances in Long-Acting Antiviral Agents: Innovations in Design and Strategies for Extended Duration.

Long-acting antiviral agents present a promising strategy for overcoming the clinical challenges associated with viral infection management, such as suboptimal patient adherence, rapid viral rebound, and the emergence of resistance, while providing prolonged half-life, improved metabolic stability, and sustained drug exposure. This perspective systematically reviews recent advancements in the design and optimization of long-acting antivirals from a medicinal chemistry standpoint. We highlight key factors that contribute to sustained efficacy, including target binding kinetics, metabolic stability, depot formation, and physicochemical properties. Case studies illustrate how structural modifications can be employed to enhance systemic exposure and achieve prolonged pharmacodynamic effects. This perspective offers a comprehensive framework for the rational development of next-generation long-acting antivirals, with the aim of guiding innovations to improve treatment outcomes and patient compliance across a range of viral infections.