Ipomoeassin-F inhibits the in vitro biogenesis of the SARS-CoV-2 spike protein and its host cell membrane receptor
| Autor: | Guanghui Zong, Kwabena B Duah, Peristera Roboti, Stephen High, Sarah O'Keefe, Hayden O. Schneider, Wei Shi |
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| Rok vydání: | 2021 |
| Předmět: |
Short Report
Biology Antiviral Agents Article Viral protein biogenesis 03 medical and health sciences 0302 clinical medicine Humans Endoplasmic reticulum (ER) Receptor 030304 developmental biology Sec61 translocon Host cell membrane 0303 health sciences Chemistry SARS-CoV-2 Endoplasmic reticulum COVID-19 ER membrane complex Cell Biology Virus Internalization Cell-free translation Small molecule In vitro COVID-19 Drug Treatment Cell biology Membrane protein Spike Glycoprotein Coronavirus ER membrane complex (EMC) Host cell plasma membrane Glycoconjugates 030217 neurology & neurosurgery Biogenesis |
| Zdroj: | Journal of Cell Science article-version (VoR) Version of Record bioRxiv article-version (status) pre article-version (number) 1 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | In order to produce proteins essential for their propagation, many pathogenic human viruses, including SARS-CoV-2, the causative agent of COVID-19 respiratory disease, commandeer host biosynthetic machineries and mechanisms. Three major structural proteins, the spike, envelope and membrane proteins, are amongst several SARS-CoV-2 components synthesised at the endoplasmic reticulum (ER) of infected human cells prior to the assembly of new viral particles. Hence, the inhibition of membrane protein synthesis at the ER is an attractive strategy for reducing the pathogenicity of SARS-CoV-2 and other obligate viral pathogens. Using an in vitro system, we demonstrate that the small molecule inhibitor ipomoeassin F (Ipom-F) potently blocks the Sec61-mediated ER membrane translocation and/or insertion of three therapeutic protein targets for SARS-CoV-2 infection; the viral spike and ORF8 proteins together with angiotensin-converting enzyme 2, the host cell plasma membrane receptor. Our findings highlight the potential for using ER protein translocation inhibitors such as Ipom-F as host-targeting, broad-spectrum antiviral agents. This article has an associated First Person interview with the first author of the paper. Summary: Ipomoeassin-F blocks the Sec61-dependent translocation of SARS-CoV-2 proteins into and across the endoplasmic reticulum, highlighting the potential of Sec61 inhibitors as antiviral agents. |
| Databáze: | OpenAIRE |
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