Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. Firstly, the coronavirus 3-chymotrypsin-like protease (3CLpro) can control virus replication. Secondly, 3CLpro is responsible for cleaving Polyproteins 1a and 1ab of SARS-CoV-2.1. However, if without the activity of the SARS-CoV-2 3CLpro, it can not release structural proteins to inhibit viral replication.

On May 25, 2023, the U.S. Food and Drug Administration (FDA)approved the oral antiviral Paxlovid (Nirmatrelvir tablets and Ritonavir tablets, co-packaged for oral use) for the treatment of mild-to-moderate COVID-19 in adults. Today, we will introduce Nirmatrelvir and Ritonavir.

Nirmatrelvir (PF-07321332) is a potent and orally active 3CLpro inhibitor targeting the SARS-CoV-2 virus.

Nirmatrelvir is a reversible covalent inhibitor. Firstly, Nirmatrelvir reacts with one of the main protease’s cysteine residues. Secondly, PF-07321332 contains a nitrile warhead. We can optimize the oral delivery by the reduction of the number of H-bond donors. .

On one hand, Ritonavir is a SARS-CoV 3CLpro inhibitor with an IC50 of 1.61 μM. On the other hand, Ritonavir is an HIV protease inhibitor for the research of HIV infection and AIDS.

In a word, Nirmatrelvir (PF-07321332) is a potent and orally active 3CLpro inhibitor for the research of COVID-19.


[1]  KoenVandyck, et al. Current Opinion in Virology Available online 27 April 2021.

[2]  Macchiagodena M, et al. J Mol Graph Model. 2022;110:108042.