Macrocyclic Compounds: Unveiling Their Distinctive Antiviral Advantages in Medicinal Research

The hazards posed by viral infections are becoming increasingly severe. The expanding infected population, surging risks of outbreaks, and heightened immune evasion demand continuous structural innovation in antiviral chemical agents beyond vaccines. Macrocyclic structures have achieved remarkable success in combating HCV, drawing growing attention to their potential in antiviral applications. FDA-approved macrocyclic drugs are now being widely explored for their feasibility in broader antiviral therapies. These macrocyclic compounds employ a distinctive mechanism to effectively target multiple stages of the viral life cycle. Its unique structure endows it with greater potential as an antiviral target and better druggability. By virtue of their structural advantages, they constrain viral immune evasion and demonstrate remarkable efficacy in addressing critical clinical challenges, particularly in counteracting drug resistance. Herein, we summarize antiviral macrocyclic drugs studied over the past decade, examining their structural advantages, structure-activity relationships, and molecular mechanisms from both viral and host perspectives during the viral lifecycle.