New Advances in Small Molecules Targeted at Viral Capsid-Genome Binding

The capsid protein plays a crucial role in the viral life cycle. By interacting with the viral genome, it facilitates the assembly of the nucleocapsid, ultimately leading to the formation of the viral particle. Therefore, interfering with or disrupting the interaction between the capsid protein and viral genome can effectively inhibit viral replication and infection. This review focuses on elucidating the binding mechanisms between the capsid protein and the viral genome, as well as their potential applications as therapeutic targets. In particular, it summarizes the research progress on small-molecule drugs targeting the capsid-genome binding sites of dengue virus, HBV, and SARS-CoV-2. Notably, this review provides a detailed discussion on the mechanisms by which these small-molecule inhibitors interfere with the capsid-genome interaction, aiming to offer inspiration for the future development of novel antiviral drugs targeting the capsid-genome binding.