2'-Fluorinated nucleoside chemistry for new drug discovery: achievements and prospects.

Fluorinated nucleosides are an important class of modified nucleosides that have demonstrated therapeutic potential for treating various human diseases, especially viral infections and cancer. Many fluorinated nucleosides have advanced into clinical trials or have been approved by the FDA for use in patients. Among these fluorinated nucleosides, azvudine, developed by us, has been officially approved by the National Medical Products Administration for the treatment of coronavirus disease 2019 (COVID-19) and human immunodeficiency virus, indicating the therapeutic promise of fluorinated nucleosides. In view of the therapeutic promise of fluorinated nucleosides for antiviral and anticancer therapy, in this Review we will provide a comprehensive overview of well-established 2'-fluorinated nucleosides approved for use in the market or those in clinical stages for antiviral and antitumor therapies, highlighting the drug discovery strategies, structure-activity relationship studies, mechanisms of action, and preclinical/clinical studies and also discuss the challenges and future directions for nucleoside-based new drug discovery.