Abstract
Sphingosine has been shown to prevent and eliminate bacterial infections of the respiratory tract, but it is unknown whether sphingosine can be also employed to prevent viral infections. To test this hypothesis, we analyzed whether sphingosine regulates the infection of cultured and freshly isolated ex vivo human epithelial cells with pseudoviral particles expressing SARS–CoV-2 spike (pp-VSV–SARS–CoV-2 spike) that served as a bona fide system mimicking SARS–CoV-2 infection. We demonstrate that exogenously applied sphingosine suspended in 0.9% NaCl prevents cellular infection with pp-SARS–CoV-2 spike. Pretreatment of cultured Vero epithelial cells or freshly isolated human nasal epithelial cells with low concentrations of sphingosine prevented adhesion of and infection with pp-VSV–SARS–CoV-2 spike. Mechanistically, we demonstrate that sphingosine binds to ACE2, the cellular receptor of SARS–CoV-2, and prevents the interaction of the receptor-binding domain of the viral spike protein with ACE2. These data indicate that sphingosine prevents at least some viral infections by interfering with the interaction of the virus with its receptor. Our data also suggest that further preclinical and finally clinical examination of sphingosine is warranted for potential use as a prophylactic or early treatment for coronavirus disease-19.
Highlights
Infections with a novel member of the Coronaviridae family, named severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), are a serious global health problem and are responsible for the coronavirus disease 2019 (COVID-19) pandemic
The results show that sphingosine dose-dependently prevented the infection with pp-vesicular stomatitis virus (VSV)–SARS–CoV-2 spike (Fig. 1A)
Our results demonstrate that exogenous sphingosine prevents infection of cultured epithelial cells and, most importantly, freshly isolated human nasal epithelial cells with ppVSV-SARS-CoV-2 spike
Summary
Infections with a novel member of the Coronaviridae family, named severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), are a serious global health problem and are responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS–CoV-2 infects cells by the initial interaction of the surface unit S1 of the viral spike glycoprotein with its cellular receptor angiotensin-converting enzyme 2 (ACE2) [3,4,5,6]. The studies showed that these particles accurately reflect key aspects of the entry of coronavirus into host cells [3]; in particular they bind to ACE2 for infectious entry, which was inhibited by anti-ACE2 antibodies. This system allows a safe and easy method to study principle biomedical questions of SARS–CoV-2 infections. EDITORS' PICK: Sphingosine binds to ACE2 whether exogenous sphingosine could be exploited as an antiviral compound
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