Leflunomide is an immunosuppressant used as a disease-modifying drug for rheumatoid arthritis and psoriatic arthritis. Immunosuppressants are drugs that decrease the immune system and chronic inflammation of the joints. Leflunomide has an anti-rheumatic effect with a slow onset of action. It works by stabilizing the overactivity of immune system cells that cause inflammation of the joints. To do this, leflunomide inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHOH) which plays a key role in the synthesis of uridine monophosphate (rUMP), necessary for the synthesis of DNA and RNA. 

A study to examine the tolerability of high doses of leflunomide in patients with COVID-19 who are not yet hospitalized, but who have risk factors for disease progression and complications, has begun. In vitro studies have shown the antiviral effects of leflunomide against CoV-2-SARS. The hypothesis of this study is that targeting high-risk patients earlier in disease progression and a higher dose of leflunomide are necessary to see an improvement in disease outcome with COVID-19.