Targeting arachidonic acid-related metabolites in COVID-19 patients: potential use of drug-loaded nanoparticles.

In March 2020, The World Health Organization (WHO) has declared that the coronavirus disease 2019 (COVID-19) is characterized as a global pandemic. As of September 2020, infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to 213 countries and territories around the world, affected more than 31.5 million people, and caused more than 970,000 deaths worldwide. Although COVID-19 is a respiratory illness that mainly targets the lungs, it is currently well established that it is a multifactorial disease that affects other extra-pulmonary systems and strongly associated with a detrimental inflammatory response. Evidence has shown that SARS-CoV-2 causes perturbation in the arachidonic acid (AA) metabolic pathways; this disruption could lead to an imbalance between the pro-inflammatory metabolites of AA including mid-chain HETEs and terminal HETE (20-HETE) and the anti-inflammatory metabolites such as EETs and subterminal HETEs. Therefore, we propose novel therapeutic strategies to modulate the level of endogenous anti-inflammatory metabolites of AA and induce the patient's endogenous resolution mechanisms that will ameliorate the virus-associated systemic inflammation and enhance the primary outcomes in COVID-19 patients. Also, we propose that using nanoencapsulation of AA and its associated metabolites will contribute to the development of safer and more efficacious treatments for the management of COVID-19.

Subterminal hydroxyeicosatetraenoic acids: Crucial lipid mediators in normal physiology and disease states.

Cytochrome P450 (P450) enzymes are superfamily of monooxygenases that hold the utmost diversity of substrate structures and catalytic reaction forms amongst all other enzymes. P450 enzymes metabolize arachidonic acid (AA) to a wide array of biologically active lipid mediators. P450-mediated AA metabolites have a significant role in normal physiological and pathophysiological conditions, hence they could be promising therapeutic targets in different disease states. P450 monooxygenases mediate the (ω-n)-hydroxylation reactions, which involve the introduction of a hydroxyl group to the carbon skeleton of AA, forming subterminal hydroxyeicosatetraenoic acids (HETEs). In the current review, we specified different P450 isozymes implicated in the formation of subterminal HETEs in varied tissues. In addition, we focused on the role of subterminal HETEs namely 19-HETE, 16-HETE, 17-HETE and 18-HETE in different organs, importantly the kidneys, heart, liver and brain. Furthermore, we highlighted their role in hypertension, acute coronary syndrome, diabetic retinopathy, non-alcoholic fatty liver disease, ischemic stroke as well as inflammatory diseases. Since each member of subterminal HETEs exist as R and S enantiomer, we addressed the issue of stereoselectivity related to the formation and differential effects of these enantiomers. In conclusion, elucidation of different roles of subterminal HETEs in normal and disease states leads to identification of novel therapeutic targets and development of new therapeutic modalities in different disease states.