Exploratory analysis of functional lipidomics in the COVID-19 pathophysiology: molecular targets, metabolism and biochemical reprogramming due to hypoxia

Abstract

Lipids represent the majority of biomolecules comprised in metabolomics. In this sense, a functional lipidomic configures an integrative strategy for the identification of bioactive lipids, membrane lipids composition, interactions of lipids with signaling proteins and metabolism enzymes. Consequently, lipids can influence pathological processes, such as inflammation and signaling of the tissue microenvironment. COVID-19 disease, caused by the SARS-CoV-2 coronavirus, can cause mild to critical illness. The critical cases present an exacerbated inflammatory response, and the lung may be the organ most affected. Metabolic diseases are mandatory as risk factors for COVID-19, but the mechanisms related to metabolism, especially those involving lipids, remain unclear. On the other hand, SARS-CoV-2 possesses a virus capsid surrounded by a lipid bilayer and the role of lipids in a viral infection comprises the fusion of the virus membrane to the host cell until the viral replication process. In this project, we propose a multidisciplinary approach to study the functional lipidomics applied in the pathophysiological processes of COVID-19, and we will use hypoxia as a model to evaluate biochemical reprogramming in this disease. Thus, we intend to: i) describe the plasma lipid composition of patients with COVID-19 in the broad severity illness; ii) characterize cell activation/signaling and metabolism pathways in blood leukocytes; iii) obtaining the monocytes subpopulations, determining their lipid composition and gene expression by Single-cell Lipidomics; iv) using the monocyte's lipidomics data for chemical imaging (MALDI) approach in bronchoalveolar lavage matrix or lung biopsy slides; v) determine the correlation of lipid metabolism and its bioactive metabolites in the modulation of SARS-CoV-2-induced inflammation and infectivity in monocytes in vitro, and vi) consider hypoxia as a modulator of lipid metabolism (in vivo and in vitro) and determine its effects on the disease pathology. Therefore, this study will clarify the involvement of lipid species in COVID-19 development and may suggest new molecular therapeutic targets. (AU)