Fig. 1.

Impact of Ceramide-1 phosphate rheostat (Cer-1P^high/S1P^low) for controlling SARS-Cov-2 in Covid 19 disease.

a. SARS-CoV-2 utilizes ACE-II receptors on epithelial cells for its entry and replication. Activation of ACE-II receptors is associated with the activation of S1PR1 signaling which is known to promote Th2 effector immune responses and subsequent fibrosis. Activation of Sphingosine kinase 1 (SK1) is believed to promote viral replication in ERK-1/2, MAPK and AKT dependent manner in lipid rafts and endosomal compartment. Blocking SK1 activity or use of S1P analogue (FTY720) can lower down infection induced cytokine storm / fibrosis. This is anticipated to protect severely infected patients from harmful inflammatory response even after virus is cleared. b. Mobilizing Ceramide-1 phosphate in the host by Ceramide Kinase (discussed in the text) represent another potential strategy for controlling SARS-CoV-2 infection by its potential of enhancing autophagy, M1 retuning of Th2/17 programmed macrophages and MHC-I restricted viral antigen presentation by M1 macrophages to CTL for augmenting M1 / Th1 programming in the host. Combining Ceramide-1 Phosphate can repurpose Remedsvir / Tocilizumab and polarize Th17 response towards Th1 and mitigate fibrosis for effective eradication of viral burden in lungs. High C1P and low S1P rheostat is anticipated to promote M1/ Th1 programming inhibit pulmonary fibrosis and Th17 programming of lung which is pathogenic in nature and contribute to the infected related death. This will afford help immune system to inhibit replication of virus effectively and contribute to anti-Covid-19 responses.