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

• Published in: Chemical & pharmaceutical bulletin Vol. 70; no. 3; pp. 199 - 201
• Main Authors: Hasegawa, Tsukasa, Imamura, Riyo M., Suzuki, Tateki, Hashiguchi, Takao, Nomura, Takao, Otsuguro, Satoko, Maenaka, Katsumi, Sasaki, Michihito, Orba, Yasuko, Sawa, Hirofumi, Sato, Akihiko, Okabe, Takayoshi, Nagano, Tetsuo, Kojima, Hirotatsu
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.03.2022; Japan Science and Technology Agency
• Subjects: acoustic ejection MS; Acoustics; Antiviral activity; Antiviral drugs; Coronaviruses; COVID-19 - drug therapy; High-throughput screening; High-Throughput Screening Assays - methods; Humans; label-free; main protease; Protease; Protease inhibitors; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; Proteinase inhibitors; SARS-CoV-2; Screening; Severe acute respiratory syndrome coronavirus 2; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease; Substrates; acoustic ejection MS; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease; label-free; main protease; high-throughput screening
• ISSN: 0009-2363; 1347-5223; 1347-5223
• DOI: 10.1248/cpb.c21-01003

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.