https://www.socictopen.socict.org/files/original/b66b2601e3c608024cc623c8ea73ac99.pdf 131c59c559ef1ae963cad0f0b37be548 Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Coronavirus Description An account of the resource Dominio científico: Coronavirus Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells. Creator An entity primarily responsible for making the resource Barbara Gripp, Katrin Anne Becker, Alexander Carpinteiro, Markus Hoffmann, Stefan Pöhlmann, Nicolas Hoertel, Michael J Edwards, Markus Kamler, Johannes Kornhuber, Erich Gulbins Description An account of the resource The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance rhinovirus or SARS-CoV-2. Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, i.e. trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol, a mucolytic drug applied by inhalation, suggests that the drug might inhibit the acid sphingomyelinase, and thereby infection with SARS-CoV-2. To test this, we used spike protein pseudotyped viral particles (pp-VSV-SARS-CoV-2 spike), a bona fide system for mimicking SARS-CoV-2 entry into cells. Viral uptake and formation of ceramide localization were determined by fluorescence microscopy, activity of the acid sphingomyelinase by consumption of [14C]sphingomyelin and ceramide was quantified by a kinase method. We found that entry of pp-VSV-SARS-CoV-2 spike required activation of acid sphingomyelinase and release of ceramide, events that were all prevented by pretreatment with ambroxol. We also obtained nasal epithelial cells from human volunteers prior to and after inhalation of ambroxol. Inhalation of ambroxol reduced acid sphingomyelinase activity in nasal epithelial cells, and prevented pp-VSV-SARS-CoV-2 spike-induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo. The addition of purified acid sphingomyelinase or C16 ceramide restored entry of pp-VSV-SARS-CoV-2 spike into ambroxol-treated epithelial cells. We propose that ambroxol might be suitable for clinical studies to prevent COVID-19. Date A point or period of time associated with an event in the lifecycle of the resource 2021 Subject The topic of the resource infection, SARS-CoV-2, ambroxol, acid sphingomyelinase, ceramide, human nasal epithelial cells Identifier An unambiguous reference to the resource within a given context 10.1016/j.jbc.2021.100701 Source A related resource from which the described resource is derived The Journal of biological chemistry