Product Spotlight: Effect of COVID-19 on Eicosanoids & Prostaglandins

Posted on April 12, 2021

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The Effect of COVID-19 on Lipid Inflammation Mediators

If you have read some of our earlier blogs, you know that lipids are playing a key role in fighting against COVID-19. Lipids are being used as adjuvants and as drug delivery nanotechnology in COVID-19 vaccines, but vaccine technology isn’t the only way that lipid research is being utilized in the fight against COVID-19.

Lipids play a key role in many cellular systems as they are a major components of cell membranes and key cellular energy sources. Arachidonic acid (AA) is produced when the COVID-19 virus induces the plasma membrane to secrete phospholipase 2 (cPLA2). AA is then converted to pro-inflammatory lipid mediators such as prostaglandins (PGs), thromboxanes (TXA2), leukotrienes (LTs), and other eicosanoids via three metabolic pathways. PGs and TXA2 are synthesized via the cyclooxygenase (COX) pathway, and LTs are synthesized via the lipoxygenase (LOX) pathway. The cytochrome P450 (CYP) pathway is responsible for converting AA to other eicosanoids that have anti-inflammatory properties and can also cause an increase in inflammatory cytokines.

The COX pathway oxidizes AA into PGH2 which subsequently isomerizes to form other PGs such as PGE2 and PGD2. PGE2 is just one of the PGs responsible for the inflammatory process. Several studies have shown that PGE2 can raise viral pathogens by interacting with viral transcriptions and translations. The SARS-CoV outbreak of 2003 was shown to increase the production of PGE2 by binding to COX-2. This happens in many viral infections including RSV and HSV. Elevated levels of PGE2 in males, older patients, and patients with comorbidities such as obesity may be an explanation for these groups' hypersensitivity to COVID-19.

The LOX pathway, specifically the 5-LOX pathway, is involved in viral pathophysiology. LTs are produced through the 5-LOX pathway and unlike PGE2 have both pro-and anti-inflammatory properties. High levels of LTs, specifically LTB4, can cause hyperimmune and inflammation reactions in COVID-19 progression. Oral or intravenous administration of these eicosanoids may increase the recovery or chances of avoiding the viral infection altogether.

CYP is the prospective third branch of the AA metabolic cascade. CYP hydroxylase enzymes can convert AA to hydroxyeicosatetraenoic acids (HETEs). CYP epoxygenase enzymes catalyze the epoxidation of AA to form epoxyeicosatrienoic acids (EETs). EETs possess anti-inflammatory activity while HETEs increase inflammatory cytokines and adhesion molecules for vasoactive compounds. EETs are further metabolized in a separate pathway to form biologically inactive compounds that can be secreted such as dihydroxyeicosatrienoic acids (DHETs), dihydroxyeicosatetraenoic acids (DHEQs), and dihydroxyeicosapentanoic acids (DiHDPAs).

Several strategies have been proposed for managing COVID-19 by either blocking or stimulating specific inflammatory pathways. One such method uses bioactive lipids such as AA as an antiviral medication or other omega-3 fatty acid-derived lipids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to resolve inflammation. COX-2 inhibitors (COXIBs) are another proposed COVID-19 management tool that could offer anti-inflammatory properties and cardiovascular protection. Small-molecule inhibitors directed at the inhibition of cPLA2 have been proposed to decrease the synthesis of COVID-19 RNA. Other therapies have been proposed that are directed at cytokines such as recombinant IFN antiviral treatment, cytokine blockades, and specialized pro-resolving mediators.

The hyperinflammatory state associated with COVID-19 is caused by the hyperactivity of inflammation pathways related to the AA cascade. Understanding the causal relationship between AA metabolites such as prostaglandins and leukotrienes and the severity of COVID-19 symptoms exhibited by infected persons is a major step toward determining effective COVID-19 management therapies.

This is just one example of how Eicosanoids and Prostaglandins are being studied in human pathology. We invite you to discover the difference that Avanti’s selection of ultra-pure eicosanoids and prostaglandins can make in your research today!

Can't find the perfect product for your research? We are happy to custom synthesize it for you! Contact Us today!

To read more about the "Role of Arachidonic Cascade in COVID-19 Infection" and see images of all the pathways mentioned, click HERE.