Pfizer's Paxlovid: Method of Action
Jan 17, 2022
Health Canada announced they have approved Pfizer’s antiviral treatment for COVID-19, PAXLOVID ™. This drug is a combination of Pfizer’s investigational antiviral PF-07321332 (Nirmatrelvir) and a low dose of Ritonavir, an antiretroviral medication commonly used to treat HIV. The drug can be used on adult patients with mild or moderate COVID-19 who are at high risk for serious illness.
Paxlovid is administered orally, giving patients the ability to take it in the comfort of their home. In patients who were given Paxlovid within three days of symptom onset, COVID-19 associated hospitalizations or deaths were reduced by 89%. In the placebo group there were sadly 10 deaths reported, and in the test group there were zero deaths reported.
3-Chymotrypsin-like protease, also known as 3CL-like protease, is the main protease found in coronaviruses. It cleaves the coronavirus polyprotein at 11 conserved sites prior to translation into viral RNA. Nirmatrelvir works by covalently binding to 3CL-like proteases and forming a thioimidate adduct between the drug’s nitrile site and the protease’s catalytic cysteine. This ultimately disrupts the replication of COVID-19 in vivo.
Ritonavir is a CYP inhibitor that acts on CYP3A enzymes, which are responsible for the metabolism of Nirmatrelvir. When Ritonavir is taken with Nirmatrelvir, this mechanism increases the plasma concentration of Nirmatrelvir, extending its half-life to 6.05 hours. Due to CYP3A enzymes being a common metabolic enzyme for drugs in the liver, there are many drug interactions found with Ritonavir.
Further reading:
https://go.drugbank.com/drugs/DB00503
https://go.drugbank.com/drugs/DB16691