The ongoing COVID-19 pandemic caused by the SARS-CoV-2 virus and its variants represents a once in a century public health disaster that continues to impact mankind, as well as the global economy. The disease has created an urgent need for rapid development of both preventative measures (e.g., vaccines) and post-infection treatment options. Both aims have been achieved in record time, the latter initially being driven by investigations into repurposing existing drugs, which has produced relatively few effective treatment options. The search for novel SARS-CoV-2 antivirals, on the other hand, has led to the development of molnupiravir by Merck, EDP-235 by Enanta, S-217622 by Shionogi, and several others. The first such antiviral to receive approval by the FDA, Paxlovid, is an orally-active combination of the SARS-CoV-2 main protease inhibitor nirmatrelvir (1; PF-07321332) and the HIV antiviral ritonavir, disclosed by Pfizer in late 2021. This drug combination was shown to reduce risk of progression to severe COVID-19 in high-risk, symptomatic patients by 89% compared to placebo, exemplifying the crucial role the drug is expected to play worldwide in the continuing efforts to combat the COVID-19 pandemic.