Antiviral strategies against H5N1: current options and emerging therapeutics.

Highly pathogenic avian influenza A(H5N1) continues to pose a significant threat to global health due to its increasing geographic spread, high mortality in human cases, and expanding host range, including recent mammalian infections. Antiviral therapy remains a key strategy alongside vaccination, especially for controlling outbreaks and limiting disease severity. This article provides a comprehensive, up-to-date overview of antiviral agents with established or investigational activity against H5N1, including both globally approved drugs and regionally licensed compounds, such as arbidol and triazavirin in Russia and laninamivir and favipiravir in Japan. We detail the mechanisms of action, approval status, resistance patterns, and efficacy data in H5N1-specific models. The recent regulatory approvals of onradivir, suraxavir marboxil, and ZX-7101A in China are highlighted, along with emerging antivirals in advanced development. We summarize findings from relevant clinical trials and discuss key resistance-associated mutations identified in recent H5N1 isolates. Although several agents show promise in preclinical studies, clinical data specifically for H5N1 remain nonexistent. Challenges persist around resistance monitoring, access to novel therapies, and regulatory harmonization. Expanding the antiviral armamentarium through accelerated evaluation and integration of both traditional and innovative compounds will be essential to pandemic preparedness and effective H5N1 outbreak response.