Abstract Retinoic acid-inducible gene-I (RIG-I) plays a pivotal role in recognizing and combating RNA viruses in humans, and it has become a drug target of significant interest. RIG-I agonists composed of dsRNA represent antiviral and antitumor therapies, however the development of small-molecule RIG-I agonists, with their potential for improved pharmacokinetics, remains an unmet need. Here, we report small-molecule RIG-I agonists that directly activate the RIG-I receptor protein.
