Small-Molecule Strategies against Human Adenoviruses: Progress, Challenges, and Future Perspectives

Area of Science:

• Virology and Medicinal Chemistry
• Antiviral Drug Discovery

Background:

• Human adenoviruses (HAdVs) pose a significant health risk, particularly to immunocompromised individuals, often leading to severe, life-threatening conditions.
• Current treatments for HAdV infections lack FDA approval, and existing options like cidofovir have limitations including toxicity and resistance, highlighting the need for new therapies.

Purpose of the Study:

• To critically evaluate recent advancements in the development of small-molecule antiviral drugs targeting human adenovirus infections.
• To discuss innovative screening methodologies and host-targeted strategies for optimizing anti-HAdV drug discovery.

Main Methods:

• Review and analysis of recent literature on small-molecule anti-HAdV drug development.
• Evaluation of promising molecular scaffolds, screening techniques, and host-targeted approaches.
• Integration of medicinal chemistry, virology, and pharmacology insights.

Main Results:

• Identification of promising molecular scaffolds and innovative screening methodologies in small-molecule anti-HAdV drug development.
• Emphasis on exploring diverse chemical spaces and combining structure-based design with high-throughput phenotypic screening.
• Discussion of host-targeted strategies as a viable alternative to direct antiviral agents.

Conclusions:

• There is an urgent need for novel, safer, and more effective antiviral therapies against human adenoviruses.
• Integrating diverse chemical exploration, advanced screening, and structure-based design is key to accelerating anti-HAdV drug discovery.
• Strategic considerations are discussed to facilitate the translation of next-generation HAdV therapeutics into clinical practice.