A drug screening toolkit based on the -1 ribosomal frameshifting of SARS-CoV-2

Yanqiong Chen; Huan Tao; Silan Shen; Zhiyong Miao; Lili Li; Yongqian Jia; Hu Zhang; Xiufeng Bai; Xinyuan Fu

doi:10.1016/j.heliyon.2020.e04793

A drug screening toolkit based on the -1 ribosomal frameshifting of SARS-CoV-2

Heliyon. 2020 Aug;6(8):e04793. doi: 10.1016/j.heliyon.2020.e04793. Epub 2020 Aug 26.

Authors

Yanqiong Chen^{1

2

3}, Huan Tao⁴, Silan Shen^{5

3}, Zhiyong Miao^{1

3}, Lili Li^{5

3}, Yongqian Jia⁴, Hu Zhang^{5

3}, Xiufeng Bai^{1

3}, Xinyuan Fu^{1

3}

Affiliations

¹ Laboratory of Human Disease and Immunotherapies, West China Hospital, Sichuan University, Chengdu, China.
² National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
³ Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
⁴ Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China.
⁵ Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.

Abstract

The -1 ribosomal frameshifting is vital for the translation of the open reading frame (ORF)1b in SARS-CoV-2. The products of ORF1b participate in viral replication. Therefore, changing the frameshift frequency reduces the survival of the virus. This study aimed to successfully develop a toolkit for screening antiviral drugs. Finally, the FDA-approved drug library was screened, revealing that ivacaftor and (-)-Huperzine A worked well in changing the -1 ribosomal frameshifting of SARS-CoV-2 in vitro.

Keywords: -1 ribosomal frameshifting; Biomedical engineering; Drug screen; Microbial biotechnology; Molecular biology; Peptides; Protein engineering; SARS-Cov-2; Virology.