Lufotrelvir Explained

Lufotrelvir (PF-07304814) is an antiviral drug developed by Pfizer which acts as a 3CL protease inhibitor.^[1] It is a prodrug with the phosphate group being cleaved in vivo to yield the active agent PF-00835231.^[2] Lufotrelvir is in human clinical trials for the treatment of COVID-19, and shows good activity against COVID-19 including several variant strains, but unlike the related drug nirmatrelvir it is not orally active and must be administered by intravenous infusion, and so has been the less favoured candidate for clinical development overall.^{[3] [4] [5]}

See also

• 3CLpro-1
• Bemnifosbuvir
• Baloxavir marboxil
• Favipiravir
• GC376
• GRL-0617
• Molnupiravir
• Remdesivir
• Ribavirin
• Rupintrivir
• S-217622
• Triazavirin

Notes and References

1. Hoffman RL, Kania RS, Brothers MA, Davies JF, Ferre RA, Gajiwala KS, He M, Hogan RJ, Kozminski K, Li LY, Lockner JW, Lou J, Marra MT, Mitchell LJ, Murray BW, Nieman JA, Noell S, Planken SP, Rowe T, Ryan K, Smith GJ, Solowiej JE, Steppan CM, Taggart B . 6 . Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19 . Journal of Medicinal Chemistry . 63 . 21 . 12725–12747 . November 2020 . 33054210 . 7571312 . 10.1021/acs.jmedchem.0c01063 .
2. Boras B, Jones RM, Anson BJ, Arenson D, Aschenbrenner L, Bakowski MA, Beutler N, Binder J, Chen E, Eng H, Hammond H, Hammond J, Haupt RE, Hoffman R, Kadar EP, Kania R, Kimoto E, Kirkpatrick MG, Lanyon L, Lendy EK, Lillis JR, Logue J, Luthra SA, Ma C, Mason SW, McGrath ME, Noell S, Obach RS, O' Brien MN, O'Connor R, Ogilvie K, Owen D, Pettersson M, Reese MR, Rogers TF, Rosales R, Rossulek MI, Sathish JG, Shirai N, Steppan C, Ticehurst M, Updyke LW, Weston S, Zhu Y, White KM, García-Sastre A, Wang J, Chatterjee AK, Mesecar AD, Frieman MB, Anderson AS, Allerton C . 6 . Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19 . Nature Communications . 12 . 1 . 6055 . October 2021 . 34663813 . 8523698 . 10.1038/s41467-021-26239-2 . 2021NatCo..12.6055B .
3. de Vries M, Mohamed AS, Prescott RA, Valero-Jimenez AM, Desvignes L, O'Connor R, Steppan C, Devlin JC, Ivanova E, Herrera A, Schinlever A, Loose P, Ruggles K, Koralov SB, Anderson AS, Binder J, Dittmann M . 6 . A comparative analysis of SARS-CoV-2 antivirals characterizes 3CL^pro inhibitor PF-00835231 as a potential new treatment for COVID-19 . Journal of Virology . 95 . 7 . March 2021 . 33622961 . 8139662 . 10.1128/JVI.01819-20 .
4. Baig MH, Sharma T, Ahmad I, Abohashrh M, Alam MM, Dong JJ . Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study . Molecules . 26 . 6 . 1678 . March 2021 . 33802860 . 8002701 . 10.3390/molecules26061678 . free .
5. Vandyck K, Deval J . Considerations for the discovery and development of 3-chymotrypsin-like cysteine protease inhibitors targeting SARS-CoV-2 infection . Current Opinion in Virology . 49 . 36–40 . August 2021 . 34029993 . 8075814 . 10.1016/j.coviro.2021.04.006 .