An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19

• Published in: Science (American Association for the Advancement of Science) Vol. 374; no. 6575; pp. 1586 - 1593
• Main Authors: Owen, Dafydd R., Allerton, Charlotte M. N., Anderson, Annaliesa S., Aschenbrenner, Lisa, Avery, Melissa, Berritt, Simon, Boras, Britton, Cardin, Rhonda D., Carlo, Anthony, Coffman, Karen J., Dantonio, Alyssa, Di, Li, Eng, Heather, Ferre, RoseAnn, Gajiwala, Ketan S., Gibson, Scott A., Greasley, Samantha E., Hurst, Brett L., Kadar, Eugene P., Kalgutkar, Amit S., Lee, Jack C., Lee, Jisun, Liu, Wei, Mason, Stephen W., Noell, Stephen, Novak, Jonathan J., Obach, R. Scott, Ogilvie, Kevin, Patel, Nandini C., Pettersson, Martin, Rai, Devendra K., Reese, Matthew R., Sammons, Matthew F., Sathish, Jean G., Singh, Ravi Shankar P., Steppan, Claire M., Stewart, Al E., Tuttle, Jamison B., Updyke, Lawrence, Verhoest, Patrick R., Wei, Liuqing, Yang, Qingyi, Zhu, Yuao
• Format: Journal Article
• Language: English
• Published: United States 24.12.2021
• Subjects: Administration, Oral; Animals; Clinical Trials, Phase I as Topic; Coronavirus - drug effects; COVID-19 - drug therapy; COVID-19 - virology; Disease Models, Animal; Drug Therapy, Combination; Humans; Lactams - administration & dosage; Lactams - pharmacokinetics; Lactams - pharmacology; Lactams - therapeutic use; Leucine - administration & dosage; Leucine - pharmacokinetics; Leucine - pharmacology; Leucine - therapeutic use; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Nitriles - administration & dosage; Nitriles - pharmacokinetics; Nitriles - pharmacology; Nitriles - therapeutic use; Proline - administration & dosage; Proline - pharmacokinetics; Proline - pharmacology; Proline - therapeutic use; Randomized Controlled Trials as Topic; Ritonavir - administration & dosage; Ritonavir - therapeutic use; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Viral Protease Inhibitors - administration & dosage; Viral Protease Inhibitors - pharmacokinetics; Viral Protease Inhibitors - pharmacology; Viral Protease Inhibitors - therapeutic use; Virus Replication - drug effects

The rapid development of vaccines has been crucial in battling the ongoing COVID-19 pandemic. However, access challenges remain, breakthrough infections occur, and emerging variants present increased risk. Developing antiviral therapeutics is therefore a high priority for the treatment of COVID-19....