Paxlovid : FDA Authorizes First Oral Antiviral for Treatment of COVID-19 Tony Qu, Grade 11 Crescent School, Sunlifegene Academic Program in Medical Science SLAP COVID 19 Research Program Toronto, ON, Canada January 26,2022
With the new variant of concern, Omicron, infecting 95% of all patients with SARS-CoV-2 in the US, effective and accessible drugs are needed to prevent hospitalization and death. On December 22, the US Food and Drug Administration (FDA) officially approved the use of Paxlovid, a drug designed by Pfizer, for patients who tested positive for COVID with mild symptoms. In specific, Paxlovid contains nirmatrelvir tablets and ritonavir tablets co-packaged and prescribed to patients. Nirmatrelvir, also known as PF-07321332, is a 3-chymotrypsin-like protease (3CLpro) inhibitor. 3CLpro is an enzyme that cleaves the coronavirus polyprotein at eleven conserved sites, causing viral maturation, and hence allowing the virus to replicate. 3CLpro inhibitors were first used and demonstrated in 2018 to be effective in treating the 100% lethal feline coronavirus. In the early stages of the COVID-19 pandemic, Pfizer developed the earlier clinical candidate lufotrelvir, but the protease inhibitor drug needed to be injected strictly through intravenous therapy (IV), thus constricting its use to hospital settings. After modifying the tripeptide protein mimetic of lufotrelvir, Pfizer ended up with nirmatrelvir, and launched phase 1 clinical trial in February, 2021. Through EPIC-HR trial data, Pfizer reported positive outcomes compared to placebo. Paxlovid significantly reduced the proportion of people with COVID-19 related hospitalization or death by 88% compared to placebo among patients treated within five days of symptom onset. Ritonavir is another protease inhibitor, but was patented in 1989 and came into medical use in 1996 for HIV/AIDS. Being one of the more researched drugs, side effects such as diarrhea, nausea, and vomiting are known to scientists. Nonetheless, the FDA approved its combination with nirmatrevir in treating SARS-CoV-2. The purpose of ritonavir in Paxlovid is to help slow the metabolism, or breakdown, of nirmatrevir in order for it to remain active in the body for longer periods of time. Although nirmatrelvir is currently being supplied to hospitals worldwide, then to patients, Pfizer and other independent institutes are still monitoring its effectiveness and studying its side effects. Moreover, multiple downsides of nirmatrelvir proves it to not be a ‘wonder drug’ for this pandemic, as it is only effective in mild symptom patients and can only be used for 5 days in a row. As such, there are opportunities for pharmaceutical firms to investigate and develop other medications. In a machine learning assisted study by Jurica Novak and Vladimir Potemkin, it is shown that other 3CLpro inhibitors, including lopinavir, idoxuridine, paritaprevir, and favipiravir, also had high inhibition potentials.