Nirmatrelvir

Early work on related human rhinoviruses showed that the flexible glutamine side chain in inhibitors could be replaced by a rigid pyrrolidone.

[15] Nirmatrelvir was developed by modification of the earlier clinical candidate lufotrelvir,[16][full citation needed][17][18] which is also a covalent protease inhibitor but its active element is a phosphate prodrug of a hydroxyketone.

[22] In the co-packaged medication nirmatrelvir/ritonavir, ritonavir serves to slow the metabolism of nirmatrelvir via cytochrome enzyme inhibition, thereby increasing the circulating concentration of the main drug.

[24] In November 2021, Pfizer signed a license agreement with the United Nations–backed Medicines Patent Pool to allow nirmatrelvir to be manufactured and sold in 95 countries.

[25] Pfizer stated that the agreement will allow local medicine manufacturers to produce the pill "with the goal of facilitating greater access to the global population".

[29] A study published in March 2023 reported that treatment with nirmatrelvir within five days of initial infection reduced the risk of long COVID relative to patients who did not receive Paxlovid.

Xray crystal structure PDB:7si9
X-ray crystal structure ( PDB:7SI9 and 7VH8 ) of the SARS-CoV-2 protease inhibitor nirmatrelvir bound to the viral 3CLpro protease enzyme. Ribbon diagram of the protein with the drug shown as sticks. The catalytic residues (His41, Cys145) are shown as yellow sticks.