Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Mar 30

PMID 35352927

Authors

Yuto Unoh

Shota Uehara

Kenji Nakahara

Haruaki Nobori

Yukiko Yamatsu

Shiho Yamamoto

Yuki Maruyama

Yoshiyuki Taoda

Koji Kasamatsu

Takahiro Suto

Kensuke Kouki

Atsufumi Nakahashi

Sho Kawashima

Takao Sanaki

Shinsuke Toba

Kentaro Uemura

Tohru Mizutare

Shigeru Ando

Michihito Sasaki

Yasuko Orba

Hirofumi Sawa

Akihiko Sato

Takafumi Sato

Teruhisa Kato

Yuki Tachibana

Affiliations

Soon will be listed here.

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 , the first oral noncovalent, nonpeptidic SARS-CoV-2 3CL protease inhibitor clinical candidate. 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. exhibited antiviral activity against current outbreaking SARS-CoV-2 variants and showed favorable pharmacokinetic profiles for once-daily oral dosing. Furthermore, dose-dependently inhibited intrapulmonary replication of SARS-CoV-2 in mice, indicating that this novel noncovalent inhibitor could be a potential oral agent for treating COVID-19.

Citing Articles

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