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Evaluation of SARS-CoV-2 3C-like protease inhibitors using self-assembled monolayer desorption ionization mass spectrometry.
- Source :
-
Antiviral Research . Oct2020, Vol. 182, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
Abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic that began in 2019. The coronavirus 3-chymotrypsin-like cysteine protease (3CLpro) controls replication and is therefore considered a major target for antiviral discovery. This study describes the evaluation of SARS-CoV-2 3CLpro inhibitors in a novel self-assembled monolayer desorption ionization mass spectrometry (SAMDI-MS) enzymatic assay. Compared with a traditional FRET readout, the label-free SAMDI-MS assay offers greater sensitivity and eliminates false positive inhibition from compound interference with the optical signal. The SAMDI-MS assay was optimized and validated with known inhibitors of coronavirus 3CLpro such as GC376 (IC 50 = 0.060 μM), calpain inhibitors II and XII (IC 50 ~20–25 μM). The FDA-approved drugs shikonin, disulfiram, and ebselen did not inhibit SARS-CoV-2 3CLpro activity in the SAMDI-MS assay under physiologically relevant reducing conditions. The three drugs did not directly inhibit human β-coronavirus OC-43 or SARS-CoV-2 in vitro , but instead induced cell death. In conclusion, the SAMDI-MS 3CLpro assay, combined with antiviral and cytotoxic assessment, provides a robust platform to evaluate antiviral agents directed against SARS-CoV-2. • A novel label-free SARS-CoV-2 3CLpro enzymatic assay was developed using mass spectrometry (SAMDI-MS). • Protease inhibitors active in the SAMDI-MS assay under reducing conditions also have antiviral effects in cells. • Shikonin, disulfiram, and ebselen do not inhibit SARS-CoV-2 3CLpro in the SAMDI-MS assay. • Shikonin, disulfiram, and ebselen do not directly inhibit SARS-CoV-2 but instead are toxic to cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01663542
- Volume :
- 182
- Database :
- Academic Search Index
- Journal :
- Antiviral Research
- Publication Type :
- Academic Journal
- Accession number :
- 146073714
- Full Text :
- https://doi.org/10.1016/j.antiviral.2020.104924