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Review

Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19

1
Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, Guangdong Pharmaceutical University, Guangzhou 510080, China
2
Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
3
School of Life Sciences, University of Technology Sydney, Broadway, Sydney, NSW 2007, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7189; https://doi.org/10.3390/ijms21197189
Received: 22 August 2020 / Revised: 25 September 2020 / Accepted: 25 September 2020 / Published: 29 September 2020
The world is currently experiencing the worst health pandemic since the Spanish flu in 1918—the COVID-19 pandemic—caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world’s third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections. At present, there is neither a vaccine nor a cure for COVID-19. The severe COVID-19 symptoms of hyperinflammation, catastrophic damage to the vascular endothelium, thrombotic complications, septic shock, brain damage, acute disseminated encephalomyelitis (ADEM), and acute neurological and psychiatric complications are unprecedented. Many COVID-19 deaths result from the aftermath of hyperinflammatory complications, also referred to as the “cytokine storm syndrome”, endotheliitus and blood clotting, all with the potential to cause multiorgan dysfunction. The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed. View Full-Text
Keywords: COVID-19; SARS-CoV-2; Sphingosine kinase; sphingosine-1-phosphate; G-protein-coupled receptors COVID-19; SARS-CoV-2; Sphingosine kinase; sphingosine-1-phosphate; G-protein-coupled receptors
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MDPI and ACS Style

McGowan, E.M.; Haddadi, N.; Nassif, N.T.; Lin, Y. Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19. Int. J. Mol. Sci. 2020, 21, 7189. https://doi.org/10.3390/ijms21197189

AMA Style

McGowan EM, Haddadi N, Nassif NT, Lin Y. Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19. International Journal of Molecular Sciences. 2020; 21(19):7189. https://doi.org/10.3390/ijms21197189

Chicago/Turabian Style

McGowan, Eileen M, Nahal Haddadi, Najah T. Nassif, and Yiguang Lin. 2020. "Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19" International Journal of Molecular Sciences 21, no. 19: 7189. https://doi.org/10.3390/ijms21197189

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