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A complete response to the challenge of COVID-19 requires diagnosis, prevention, and treatment strategies. Until recently, the treatment arm has included largely ineffective, often unproven medications with minimal impact on disease outcomes. The earlier experimental therapies are now giving way to approved antiviral drugs with a demonstrated capacity for SARS-CoV-2 suppression, and more are on the way. New oral antiviral drugs will expand treatment options for persons with COVID-19 and, if used early, become the first line of defense for reducing hospitalization, mortality, and virus spread. Several oral medications have been approved for treating COVID-19 on an emergency use basis in the United States (US), European Union (EU), United Kingdom (UK), China, Russia, and India, with other countries now facilitating regulatory reviews and approvals. Here, we compare the risk/benefit profiles of three leading oral antiviral drugs: Favipiravir, Molnupiravir, and Paxlovid. These compounds have distinct features supporting their targeted use by persons with COVID-19 disease.