AbstractGlobal spread of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is still ongoing. Before an effective vaccine is available, the development of potential treatments for resultant coronavirus disease 2019 (COVID‐19) is crucial. One of the disease hallmarks is hyper‐inflammatory responses, which usually leads to a severe lung disease. Patients with COVID‐19 also frequently suffer from neurological symptoms such as acute diffuse encephalomyelitis, brain injury and psychiatric complications. The metabolic pathway of sphingosine‐1‐phosphate (S1P) is a dynamic regulator of various cell types and disease processes, including the nervous system. It has been demonstrated that S1P and its metabolic enzymes, regulating neuroinflammation and neurogenesis, exhibit important functions during viral infection. S1P receptor 1 (S1PR1) analogues including AAL‐R and RP‐002 inhibit pathophysiological responses at the early stage of H1N1 virus infection and then play a protective role. Fingolimod (FTY720) is an S1P receptor modulator and is being tested for treating COVID‐19. Our review provides an overview of SARS‐CoV‐2 infection and critical role of the SphK‐S1P‐SIPR pathway in invasion of SARS‐CoV‐2 infection, particularly in the central nervous system (CNS). This may help design therapeutic strategies based on the S1P‐mediated signal transduction, and the adjuvant therapeutic effects of S1P analogues to limit or prevent the interaction between the host and SARS‐CoV‐2, block the spread of the SARS‐CoV‐2, and consequently treat related complications in the CNS.

Frontiers in ImmunologyQ2 · MEDICINE

Battling COVID-19 Pandemic: Sphingosine-1-Phosphate Analogs as an Adjunctive Therapy?

Q2 · MEDICINE

ArticleOA

Author: Naz, Farha ; Arish, Mohd

With the sudden outbreak of COVID-19 patient worldwide and associated mortality, it is critical to come up with an effective treatment against SARS-CoV-2. Studies suggest that mortality due to COVID 19 is mainly attributed to the hyper inflammatory response leading to cytokine storm and ARDS in infected patients. Sphingosine-1-phosphate receptor 1 (S1PR1) analogs, AAL-R and RP-002, have earlier provided in-vivo protection from the pathophysiological response during H1N1 influenza infection and improved mortality. Recently, it was shown that the treatment with sphingosine-1-phosphate receptor 1 analog, CYM5442, resulted in the significant dampening of the immune response upon H1N1 challenge in mice and improved survival of H1N1 infected mice in combination with an antiviral drug, oseltamivir. Hence, here we suggest to investigate the possible utility of using S1P analogs to treat COVID-19.

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