COVID-19 Research: University Of Cincinnati Led Study Identifies Sphingosine, A Natural Body Lipid As A Potential Inhibitor Of SARS-CoV-2 And ACE2 Binding
Source: COVID-19 Research Sep 30, 2020 4 years, 1 month, 2 weeks, 9 hours, 3 minutes ago
COVID-19 Research: A study led by researchers from the University of Cincinnati along with scientists from University of Duisburg-Germany, the German Primate Center and Saarland University-Germany have discovered that sphingosine, a naturally occurring lipid in the human body could be used as a potential treatment for COVID-19 as prevents binding of SARS-CoV-2 spike to its cellular receptor ACE2.
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Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholipid.
The lipid, 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.
Inorder to test this hypothesis, the study team analyzed whether sphingosine regulates the infection of cultured and freshly isolated ex vivohuman 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.
The team demonstrated that by exogenously applying sphingosine suspended in 0.9% NaCl, it prevented cellular infection with pp-SARS-CoV-2 spike. Pre-treatment 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. The study demonstrated 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.
The study findings were published in the peer-reviewed Journal of Biological Chemistry.
https://www.jbc.org/content/early/2020/09/11/jbc.RA120.015249
The study team by examining preexisting research for other conditions, established that a lipid found in the human body could be used to prevent or treat infections with SARS-CoV-2, the virus that causes COVID-19.
The lipid, called sphingosine, is a natural element taken from the body and is important in the lipid metabolism of all cells and the local immune defense in epithelial cells, a type of cell that lines the surfaces of the body including skin, blood vessels, urinary tract and organs. They serve as a barrier between the inside and outside of your body and protect it from viruses.
Corresponding author Dr Erich Gulbins, MD, a visiting Professor in University of Cincinnati's Department of Surgery told Thailand Medical News, "We investigated whether a specific lipid is able to interfere with the binding of SARS-CoV-2 to human epithelial cells."
Dr Gulbins is also chair of the Department of Molecular Biology at the University of Duisburg-Essen, Germany.
He added, "Sphingosine has been shown in past studies to prevent and eliminate bacterial infections of the respiratory tract, but it is unknown if it can be used to prevent viral infectio
ns. The coronavirus needs to bind to specific molecules on the surface of human cells as a prerequisite to infect them.”
Dr Gulbins further added,"This is similar to the key and lock principle of a door ie to open the door you must insert the key into the lock. We show that the lipid sphingosine binds into the cellular 'lock,' the receptor ACE2, for SARS-CoV-2 and thereby prevents binding of the virus to and infection of human cells."
Researchers in this study analyzed the use of this lipid in regulating infection in cultured human cells with SARS-CoV-2 particles added.”
The study findings showed that sphingosine prevented cellular infection in these cultures, and pretreatment of cultured cells or freshly obtained human nasal epithelial cells with low concentrations of sphingosine prevented adhesion of and infection with the SARS-CoV-2 coronavirus.”
Dr Gulbins further commented, "These study findings indicate that sphingosine prevents at least some viral infection by interfering with the interaction of the virus with its receptor; it could be used as a nasal spray to prevent or treat infections with SARS-CoV-2. The nasal spray must be developed, but sphingosine is a natural product. More research is needed to see if this could be a treatment for COVID-19."
Dr Syed Ahmad, MD co-author and co-director of the University of Cincinnati Cancer Center, Professor and chief of the division of surgical oncology at University of Cincinnati and a Health surgeon, says this collaboration is particularly fascinating because it takes medical research from other areas of study and applies it to a timely public health issue.
D Ahmad the Hayden Family Endowed Chair for Cancer Research added, "The ACE2 receptor has been studied and identified as a treatment target in pancreatic cancer. This is an example of taking existing research and applying it to COVID-19 science in order to make progress in the field. This is how translational science works."
The study data indicate that sphingosine prevents at least some viral infections by interfering with the interaction of the virus with its receptor and also suggest that further preclinical and finally clinical examination of sphingosine is warranted for potential use as a prophylactic or early treatment for COVID-19.
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