期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 65, 期 9, 页码 6499-6512出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.2c00117
关键词
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S-217622 is the first oral noncovalent, nonpeptidic SARS-CoV-2 3CL protease inhibitor clinical candidate, which could be a potential oral agent for treating COVID-19.
The coronavirus disease 2019 (COVID-19) pandemic, caused bysevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted inmillions of deaths and threatens public health and safety. Despite the rapid globalspread of COVID-19 vaccines, effective oral antiviral drugs are urgently needed.Here, we describe the discovery ofS-217622, thefirst oral noncovalent,nonpeptidic SARS-CoV-2 3CL protease inhibitor clinical candidate.S-217622was discovered via virtual screening followed by biological screening of an in-house compound library, and optimization of the hit compound using a structure-based drug design strategy.S-217622exhibited antiviral activityin vitroagainstcurrent outbreaking SARS-CoV-2 variants and showed favorable pharmacokineticprofilesin vivofor once-daily oral dosing. Furthermore,S-217622dose-dependently inhibited intrapulmonary replication of SARS-CoV-2 in mice,indicating that this novel noncovalent inhibitor could be a potential oral agent fortreating COVID-19.
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