Abstract
Understanding pathways that might impact coronavirus disease 2019 (COVID-19) manifestations and disease outcomes is necessary for better disease management and for therapeutic development. Here, we analyzed alterations in sphingolipid (SL) levels upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection induced elevation of SL levels in both cells and sera of infected mice. A significant increase in glycosphingolipid levels was induced early post SARS-CoV-2 infection, which was essential for viral replication. This elevation could be reversed by treatment with glucosylceramide synthase inhibitors. Levels of sphinganine, sphingosine, GA1, and GM3 were significantly increased in both cells and the murine model upon SARS-CoV-2 infection. The potential involvement of SLs in COVID-19 pathology is discussed.
Highlights
In December 2019, the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was identified as the causative agent of a cluster of acute atypical pneumonia cases in the city of Wuhan, China (Zhou et al, 2020)
The alteration of SL levels was reflected by an elevation in the levels of many other downstream SLs; DHCer and Cer levels were significantly elevated in SARS-CoV-2-infected cells (Fig 2)
Levels of Sa, So, GA1, and GM3 were significantly increased in both cells and the murine model upon SARS-CoV-2 infection
Summary
In December 2019, the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was identified as the causative agent of a cluster of acute atypical pneumonia cases in the city of Wuhan, China (Zhou et al, 2020). There is an enormous amount of data demonstrating that it may involve multiple organ systems, including the nervous, cardiovascular, respiratory, gastrointestinal, renal, hematopoietic, and immune systems (Erdinc et al, 2021). Understanding pathological pathways involved in COVID-19 manifestations might reveal new approaches for therapeutic strategies and disease management. In addition to playing a structural role, some SLs are bioactive and control vital biological functions by regulating signal transduction pathways involved in several processes. Some bioactive SLs are implicated in pathological processes, including inflammationassociated illnesses such as atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, type II diabetes, obesity, cancer, and neurological and neurodegenerative diseases (Ogretmen, 2018; D’Angelo et al, 2019; Hussain et al, 2019; Gomez-Larrauri et al, 2020). SLs play an important role in the control of virus replication and the innate immune response (SchneiderSchaulies & Schneider-Schaulies, 2013; Schneider-Schaulies & Schneider-Schaulies, 2015; Bezgovsek et al, 2018; Yager & Konan, 2019; Melamed et al, 2020; Vitner, 2020)
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