Fluorine in Medicinal Chemistry: In Perspective to COVID-19

[Image: see text] Over two years into the outbreak of COVID-19, the quest for effective and economical drugs has become starkly clear to reduce the risk of progression of coronavirus disease. A number of drugs have been investigated, and they can be taken orally at home and be used after exposure to SARS-CoV-2 or at the first sign of COVID-19. Fluorinated oral anti-COVID-19 drugs—including Paxlovid, the first oral tablet for the treatment of COVID-19—constitute an important subgroup. Fluorine has been widely used in the pharmaceutical market and can lead to improved selectivity indices, increased lipophilicity, greater metabolic stability, and improved anti-COVID-19 efficacy. In this mini-review, we will give an update on fluorinated anti-COVID-19 drugs by providing the key information and current knowledge of these drugs, including their molecular design, metabolism and pharmacokinetics, and mechanism of action.