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.

中文翻译：

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鞘氨醇可防止SARS-CoV-2尖峰与其细胞受体ACE2结合。

鞘氨醇已显示出预防和消除呼吸道细菌感染的能力，但尚不清楚鞘氨醇是否也可用于预防病毒感染。为了验证这一假设，我们分析了鞘氨醇是否通过表达SARS–CoV-2尖峰（pp-VSV–SARS–CoV-2尖峰）的伪病毒颗粒来调节培养的和新鲜分离的离体人上皮细胞的感染。模仿SARS–CoV-2感染的系统。我们证明，悬浮在0.9％NaCl中的外源鞘氨醇可防止pp-SARS–CoV-2尖峰引起的细胞感染。用低浓度的鞘氨醇预处理培养的Vero上皮细胞或新鲜分离的人鼻上皮细胞可防止pp-VSV–SARS–CoV-2尖峰的粘附和感染。机械上，我们证明了鞘氨醇与SARS–CoV-2的细胞受体ACE2结合，并阻止了病毒刺突蛋白的受体结合域与ACE2的相互作用。这些数据表明鞘氨醇通过干扰病毒与其受体的相互作用来预防至少一些病毒感染。我们的数据还表明，需要对鞘氨醇进行进一步的临床前和最终临床检查，以潜在地用作冠状病毒病-19的预防或早期治疗。