Discovery of S-217622, a Non-Covalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19
Y. Unoh, S. Uehara, K. Nakahara, H. Nobori, Y. Yamatsu, S. Yamamoto, Y. Maruyama, Y. Taoda, K. Kasamatsu, T. Suto, K. Kouki, A. Nakahashi, S. Kawashima, T. Sanaki, S. Toba, K. Uemura, T. Mizutare, S. Ando, M. Sasaki, Y. Orba, H. Sawa, A. Sato, T. Sato, T. Kato, Y. Tachibana
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and threatens public health and safety. Despite the rapid global spread of COVID-19 vaccines, effective oral antiviral drugs are urgently needed. Here, we describe the discovery of S-217622, the first oral non-covalent, non-peptidic SARS-CoV-2 3CL protease inhibitor clinical candidate. S-217622 was 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-217622 exhibited antiviral activity in vitro against current outbreaking SARS-CoV-2 variants and showed favorable pharmacokinetic profiles in vivo for once-daily oral dosing. Furthermore, S-217622 dose-dependently inhibited intrapulmonary replication of SARS-CoV-2 in mice, indicating that this novel non-covalent inhibitor could be a potential oral agent for treating COVID-19.
02 /Specification & Classification
Click any tag to browse matching papers- Research Focus
- Approach
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Discovery of The Clinical Candidate S-892216: A Second-Generation of SARS-CoV-2 3CL Protease Inhibitor for Treating COVID-19
Yuto Unoh, Keiichiro Hirai, … Yuki Tachibana·Journal of Medicinal ChemistryPeer-reviewed·Jul 5, 2025
- Oral administration of S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and accelerates recovery from clinical aspects of COVID-19
- Development of highly potent non-covalent inhibitors of SARS-CoV-2 3CLpro
- Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19
Yongzhi Lu, Qi Yang, … Jinsai Shang·Nature CommunicationsPeer-reviewed·Nov 23, 2024
- Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-throughput Screening
- Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro