RT Journal Article SR Electronic T1 Ipomoeassin-F inhibits the in vitro biogenesis of the SARS-CoV-2 spike protein and its host cell membrane receptor JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.24.390039 DO 10.1101/2020.11.24.390039 A1 O’Keefe, Sarah A1 Roboti, Peristera A1 Duah, Kwabena B. A1 Zong, Guanghui A1 Schneider, Hayden A1 Shi, Wei Q. A1 High, Stephen YR 2020 UL http://biorxiv.org/content/early/2020/11/24/2020.11.24.390039.abstract AB 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/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.Competing Interest StatementThe authors have declared no competing interest.