Application of Acoustic Ejection MS System to High-Throughput Screening for SARS-CoV-2 3CL Protease Inhibitors

Tsukasa Hasegawa; Riyo M. Imamura; Tateki Suzuki; Takao Hashiguchi; Takao Nomura; Satoko Otsuguro; Katsumi Maenaka; Michihito Sasaki; Yasuko Orba; Hirofumi Sawa; Akihiko Sato; Takayoshi Okabe; Tetsuo Nagano; Hirotatsu Kojima

doi:10.1248/cpb.c21-01003

Communications to the Editor

Application of Acoustic Ejection MS System to High-Throughput Screening for SARS-CoV-2 3CL Protease Inhibitors

Tsukasa Hasegawa, Riyo M. Imamura, Tateki Suzuki, Takao Hashiguchi, Takao Nomura, Satoko Otsuguro, Katsumi Maenaka, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Akihiko Sato, Takayoshi Okabe, Tetsuo Nagano, Hirotatsu Kojima

Author information

Tsukasa Hasegawa
Drug Discovery Initiative, The University of Tokyo
Riyo M. Imamura
Drug Discovery Initiative, The University of Tokyo
Tateki Suzuki
Institute for Frontier Life and Medical Sciences, Kyoto University
Takao Hashiguchi
Institute for Frontier Life and Medical Sciences, Kyoto University
Takao Nomura
Faculty of Pharmaceutical Sciences, Hokkaido University
Satoko Otsuguro
Faculty of Pharmaceutical Sciences, Hokkaido University
Katsumi Maenaka
Faculty of Pharmaceutical Sciences, Hokkaido University
Michihito Sasaki
International Institute for Zoonosis Control, Hokkaido University
Yasuko Orba
International Institute for Zoonosis Control, Hokkaido University
Hirofumi Sawa
International Institute for Zoonosis Control, Hokkaido University
Akihiko Sato
International Institute for Zoonosis Control, Hokkaido University
Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd.
Takayoshi Okabe
Drug Discovery Initiative, The University of Tokyo
Tetsuo Nagano
Drug Discovery Initiative, The University of Tokyo
Hirotatsu Kojima Corresponding author
Drug Discovery Initiative, The University of Tokyo

Keywords: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease, main protease, acoustic ejection MS, high-throughput screening, label-free

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Supplementary material

2022 Volume 70 Issue 3 Pages 199-201

DOI https://doi.org/10.1248/cpb.c21-01003

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Abstract

MS is a powerful methodology for chemical screening to directly quantify substrates and products of enzymes, but its low throughput has been an issue. Recently, an acoustic liquid-handling apparatus (Echo^®) used for rapid nano-dispensing has been coupled to a high-sensitivity mass spectrometer to create the Echo^® MS system, and we applied this system to screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease inhibitors. Primary screening of 32033 chemical samples was completed in 12 h. Among the hits showing selective, dose-dependent 3CL-inhibitory activity, 8 compounds showed antiviral activity in cell-based assay.

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