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

Autor: Nandini Chaturbhai Patel, Dafydd R. Owen, Rhonda D. Cardin, Karen J. Coffman, Jean G. Sathish, Devendra K. Rai, Heather Eng, Charlotte Moira Norfor Allerton, Jack C. Lee, Britton Boras, Melissa Avery, Qingyi Yang, Eugene P. Kadar, Anthony Carlo, Annaliesa S. Anderson, Matthew R. Reese, Li Di, Jisun Lee, Lisa Aschenbrenner, Stephen Noell, Lawrence W. Updyke, Martin Pettersson, Scott A. Gibson, Matthew F. Sammons, Al E. Stewart, Yuao Zhu, Alyssa Dantonio, Stephen W. Mason, Brett L. Hurst, Ketan S. Gajiwala, Claire M. Steppan, Liuqing Wei, Patrick Robert Verhoest, Samantha Elizabeth Greasley, Simon Berritt, R. Scott Obach, RoseAnn Ferre, Ravi Shankar P. Singh, Amit S. Kalgutkar, Jonathan J. Novak, Kevin Ogilvie, Wei Liu, Jamison B. Tuttle
Rok vydání: 2021
Předmět:
Zdroj: Science. 374:1586-1593
ISSN: 1095-9203
0036-8075
DOI: 10.1126/science.abl4784
Popis: Path to another drug against COVID-19 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. Some drug candidates in clinical trials act against the viral RNA-dependent RNA polymerase, but there are other viral enzymes that have been considered good targets for inhibition by drugs. Owen et al . report the discovery and characterization of a drug against the main protease involved in the cleavage of polyproteins involved in viral replication. The drug, PF-07321332, can be administered orally, has good selectivity and safety profiles, and protects against infection in a mouse model. In a phase 1 clinical trial, the drug reached concentrations expected to inhibit the virus based on in vitro studies. It also inhibited other coronaviruses, including severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, and could be in the armory against future viral threats. —VV
Databáze: OpenAIRE
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