The Role of Sphingolipids in the Creation of Biosensors for SARS-COV-2
Introduction. Coronaviruses are enveloped RNA viruses in humans and animals that can cause acute and chronic diseases¹. SARS-CoV-2 is closely related to two bat-derived SARS-like coronaviruses¹, which all use the cellular receptor angiotensin-converting enzyme 2 (ACE2) for entry into cells¹. Nucleic acid detection is the gold standard for SARS-CoV-2 detection, screening for markers like ORF1b, N, E or S genes using RT-PCR². Viral load may already drop from peak level when an individual becomes symptomatic². Sphingosine, a common signaling molecule, has been shown to prevent and eliminate bacterial infections of the respiratory tract3. Sphingosine is positively charged at neutral or slightly acidic pH, such as on nasal, tracheal or bronchial epithelial cell surfaces. It is speculated that sphingosine binds the ACE2 negatively charged receptor3. Methods. To establish that sphingosine has protective effects, human vero epithelial cells were treated with sphingosine for 30 minutes then infected with pp-VSV-SARS-CoV-2 spike, with Western blot to determine whether ACE2 directly bound the sphingosine3. HPLC-MS/MS lipidomics and fluorescent substrate with liquid chromatography tandem-mass spectrometry (LC-MS/MS) were used to review sphingosine levels4 and sphingolipid enzyme metabolism5 respectively. With few ways recorded in literature for quantifying sphingolipids, fluorescent polymers were developed to show sphingosine-1-phosphate (S1P) levels using molecularly imprinted polymers, with function akin to antibodies6. Results. Treatment of human nasal epithelial cells with sphingosine prevented adhesion of and infection with the COVID-19 spike particles by binding ACE2, reducing viral infection3. Sphingosine levels were correlated to infection severity: sphingosine levels below 8.3 pmol/5 × 10−5 L were highly associated with symptomatic COVID-19 (99.24%) and those with COVID-19 positive antibodies who had sphingosine levels between 8.4-23.25 pmol/5 × 10−5 serum were (99.2–99.9%) likely be asymptomatic4. Sphingolipid metabolism was also affected in a severity-dependent manner, with increased activity in ceramide producing enzymes and decreased activity in ceramide reducing enzymes5. For S1P detection, the probes had short response times and good lipid recognition in human serum6. Conclusions. As suggested by previous studies, the maintenance of optimal sphingolipid metabolism can mean the difference between symptomatic and asymptomatic infection. There is also evidence that COVID-19 infection may alter sphingolipid metabolism, making an individual more prone to a more severe disease course, suggesting that the mechanisms behind altered sphingolipid metabolism may be important for diagnostic, prognostic and therapeutic purposes3.
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- Edwards , Becker K., et al. Sphingosine prevents binding of SARS–CoV-2 spike to its cellular receptor ACE2. Journal of Biological Chemistry 2020;295(45). DOI: https://doi.org/10.1074/jbc.RA120.015249
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- Muhle , Kremer A., et al. COVID-19 and its clinical severity are associated with alterations of plasma sphingolipids and enzyme activities of sphingomyelinase and ceramidase. medRxiv 2022.01.19.22269391; doi: https://doi.org/10.1101/2022.01.19.22269391
- Li Q, Shinde S, Grasso G, et Selective detection of phospholipids using molecularly imprinted fluorescent sensory core-shell particles. Sci Rep 10, 9924 (2020). https://doi.org/10.1038/s41598-020-66802-3