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A Novel Frameshifting Inhibitor Having Antiviral Activity against Zoonotic Coronaviruses
| Content Provider | MDPI |
|---|---|
| Author | Ahn, Dae-Gyun Yoon, Gun Young Lee, Sun Hee Ku, Keun Bon Kim, Chonsaeng Kim, Kyun-Do Kwon, Young-Chan Kim, Geon-Woo Kim, Bum-Tae Kim, Seong-Jun |
| Copyright Year | 2021 |
| Description | Recent outbreaks of zoonotic coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have caused tremendous casualties and great economic shock. Although some repurposed drugs have shown potential therapeutic efficacy in clinical trials, specific therapeutic agents targeting coronaviruses have not yet been developed. During coronavirus replication, a replicase gene cluster, including RNA-dependent RNA polymerase (RdRp), is alternatively translated via a process called -1 programmed ribosomal frameshift (−1 PRF) by an RNA pseudoknot structure encoded in viral RNAs. The coronavirus frameshifting has been identified previously as a target for antiviral therapy. In this study, the frameshifting efficiencies of MERS-CoV, SARS-CoV and SARS-CoV-2 were determined using an in vitro −1 PRF assay system. Our group has searched approximately 9689 small molecules to identify potential −1 PRF inhibitors. Herein, we found that a novel compound, 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline (KCB261770), inhibits the frameshifting of MERS-CoV and effectively suppresses viral propagation in MERS-CoV-infected cells. The inhibitory effects of 87 derivatives of furo[2,3-b]quinolines were also examined showing less prominent inhibitory effect when compared to compound KCB261770. We demonstrated that KCB261770 inhibits the frameshifting without suppressing cap-dependent translation. Furthermore, this compound was able to inhibit the frameshifting, to some extent, of SARS-CoV and SARS-CoV-2. Therefore, the novel compound 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline may serve as a promising drug candidate to interfere with pan-coronavirus frameshifting. |
| Starting Page | 1639 |
| e-ISSN | 19994915 |
| DOI | 10.3390/v13081639 |
| Journal | Viruses |
| Issue Number | 8 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-08-18 |
| Access Restriction | Open |
| Subject Keyword | Viruses Virology Frameshifting Mers-cov Sars-cov-2 Coronavirus Inhibitor |
| Content Type | Text |
| Resource Type | Article |
