Nirmatrelvir yog ib qho inhibitor ntawm SARS-CoV-2 lub ntsiab protease (Mpro), kuj hu ua 3C-zoo li protease (3CLpro) lossis nsp5 protease. Inhibition ntawm SARS-CoV-2 Mpro renders nws tsis muaj peev xwm ua cov polyprotein precursors, tiv thaiv tus kab mob replication.

Nirmatrelvir inhibited cov kev ua ntawm recombinant SARS-CoV-2 Mpro nyob rau hauv ib tug biochemical assay ntawm concentrations ua tau nyob rau hauv vivo. Nirmatrelvir tau pom los khi ncaj qha rau SARS-CoV-2 Mpro active site los ntawm X-ray crystallography.

Ritonavir yog HIV-1 protease inhibitor tab sis tsis ua haujlwm tawm tsam SARS-CoV-2 Mpro. Ritonavir inhibits CYP3A-mediated metabolism ntawm nirmatrelvir, uas ua rau muaj zog plasma concentrations ntawm nirmatrelvir.

Cov tshuaj no raug pom zoo. Nws tau raug tso cai siv thaum muaj xwm txheej ceev los ntawm FDA rau kev kho mob ntawm tus kab mob me me mus rau nruab nrab tus mob coronavirus (COVID-19) rau cov neeg laus thiab cov neeg mob menyuam yaus (hnub nyoog 12 xyoos thiab laus dua qhov hnyav tsawg kawg 40 kilograms lossis txog 88 phaus) nrog Cov txiaj ntsig zoo ntawm kev kuaj SARS-CoV-2 ncaj qha, thiab leej twg muaj kev pheej hmoo siab rau kev kis mus rau COVID-19 hnyav, suav nrog kev mus pw hauv tsev kho mob lossis tuag. Nirmatrelvir / ritonavir yuav tsum tau pib sai li sai tau tom qab kuaj pom tus kab mob COVID-19 thiab nyob rau hauv tsib hnub ntawm cov tsos mob tshwm sim.

Cov lus pom zoo yog ua raws li EPIC-HR, Phase2/3 randomized soj ntsuam kev sim tshuaj ntsuam xyuas qhov ua tau zoo ntawm nirmaltrelivir/ritonavir vs. placebo hauv kev txo qis hauv tsev kho mob thiab lossis tuag txog hnub 28. Kev siv nirmaltrelivir/ritonavir hauv 5 hnub ntawm cov tsos mob tshwm sim hauv Cov tib neeg uas muaj kev pheej hmoo rau kev kis tus kab mob hnyav txo qhov kev pheej hmoo ntawm kev mus pw hauv tsev kho mob lossis tuag txog 28 hnub los ntawm 88%.