High-Throughput Screening for a SARS-CoV-2 Frameshifting Inhibitor Using a Cell-Free Protein Synthesis System

Programmed-1 ribosomal frameshifting (-1 PRF) is a translational mechanism adopted by some viruses, including SARS-CoV-2. To find a compound that can inhibit -1 PRF in SARS-CoV-2, we set up a high-throughput screening system using a HeLa cell extract-derived cell-free protein synthesis (CFPS) system...

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Main Authors: Kodai Machida, Rin Tanaka, Seraya Miki, Shotaro Noseda, Mayumi Yuasa-Sunagawa, Hiroaki Imataka
Format: Article
Language:English
Published: Taylor & Francis Group 2024-04-01
Series:BioTechniques
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Online Access:https://www.tandfonline.com/doi/10.2144/btn-2023-0102
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author Kodai Machida
Rin Tanaka
Seraya Miki
Shotaro Noseda
Mayumi Yuasa-Sunagawa
Hiroaki Imataka
author_facet Kodai Machida
Rin Tanaka
Seraya Miki
Shotaro Noseda
Mayumi Yuasa-Sunagawa
Hiroaki Imataka
author_sort Kodai Machida
collection DOAJ
description Programmed-1 ribosomal frameshifting (-1 PRF) is a translational mechanism adopted by some viruses, including SARS-CoV-2. To find a compound that can inhibit -1 PRF in SARS-CoV-2, we set up a high-throughput screening system using a HeLa cell extract-derived cell-free protein synthesis (CFPS) system. A total of 32,000 compounds were individually incubated with the CFPS system programmed with a -1 PRF-EGFP template. Several compounds were observed to decrease the -1 PRF-driven fluorescence, and one of them had some suppressive effect on -1 PRF of a SARS-CoV-2 genome sequence in transfected cells. Thus the CFPS system can be used as a tool for a high-throughput screening of chemicals.
format Article
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issn 0736-6205
1940-9818
language English
publishDate 2024-04-01
publisher Taylor & Francis Group
record_format Article
series BioTechniques
spelling doaj-art-7aeabe3ef8ea485eb824b825ecaed0032025-08-20T01:47:21ZengTaylor & Francis GroupBioTechniques0736-62051940-98182024-04-0176416116810.2144/btn-2023-0102High-Throughput Screening for a SARS-CoV-2 Frameshifting Inhibitor Using a Cell-Free Protein Synthesis SystemKodai Machida0Rin Tanaka1Seraya Miki2Shotaro Noseda3Mayumi Yuasa-Sunagawa4Hiroaki Imataka5Department of Applied Chemistry,Graduate School of Engineering, University of Hyogo, Himeji, 671-2201, JapanDepartment of Applied Chemistry,Graduate School of Engineering, University of Hyogo, Himeji, 671-2201, JapanDepartment of Applied Chemistry,Graduate School of Engineering, University of Hyogo, Himeji, 671-2201, JapanDepartment of Applied Chemistry,Graduate School of Engineering, University of Hyogo, Himeji, 671-2201, JapanDepartment of Applied Chemistry,Graduate School of Engineering, University of Hyogo, Himeji, 671-2201, JapanDepartment of Applied Chemistry,Graduate School of Engineering, University of Hyogo, Himeji, 671-2201, JapanProgrammed-1 ribosomal frameshifting (-1 PRF) is a translational mechanism adopted by some viruses, including SARS-CoV-2. To find a compound that can inhibit -1 PRF in SARS-CoV-2, we set up a high-throughput screening system using a HeLa cell extract-derived cell-free protein synthesis (CFPS) system. A total of 32,000 compounds were individually incubated with the CFPS system programmed with a -1 PRF-EGFP template. Several compounds were observed to decrease the -1 PRF-driven fluorescence, and one of them had some suppressive effect on -1 PRF of a SARS-CoV-2 genome sequence in transfected cells. Thus the CFPS system can be used as a tool for a high-throughput screening of chemicals.https://www.tandfonline.com/doi/10.2144/btn-2023-0102cell-free protein synthesisdrug discoveryprogrammed-1 ribosomal frameshiftingSARS-CoV-2screening
spellingShingle Kodai Machida
Rin Tanaka
Seraya Miki
Shotaro Noseda
Mayumi Yuasa-Sunagawa
Hiroaki Imataka
High-Throughput Screening for a SARS-CoV-2 Frameshifting Inhibitor Using a Cell-Free Protein Synthesis System
BioTechniques
cell-free protein synthesis
drug discovery
programmed-1 ribosomal frameshifting
SARS-CoV-2
screening
title High-Throughput Screening for a SARS-CoV-2 Frameshifting Inhibitor Using a Cell-Free Protein Synthesis System
title_full High-Throughput Screening for a SARS-CoV-2 Frameshifting Inhibitor Using a Cell-Free Protein Synthesis System
title_fullStr High-Throughput Screening for a SARS-CoV-2 Frameshifting Inhibitor Using a Cell-Free Protein Synthesis System
title_full_unstemmed High-Throughput Screening for a SARS-CoV-2 Frameshifting Inhibitor Using a Cell-Free Protein Synthesis System
title_short High-Throughput Screening for a SARS-CoV-2 Frameshifting Inhibitor Using a Cell-Free Protein Synthesis System
title_sort high throughput screening for a sars cov 2 frameshifting inhibitor using a cell free protein synthesis system
topic cell-free protein synthesis
drug discovery
programmed-1 ribosomal frameshifting
SARS-CoV-2
screening
url https://www.tandfonline.com/doi/10.2144/btn-2023-0102
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