Abstract
Coronaviruses have lipid envelopes required for their activity. The fact that coronavirus infection provokes the formation of cubic membranes (CM) (denoted also as convoluted membranes) in host cells has not been rationalized in the development of antiviral therapies yet. In this context, the role of bioactive plasmalogens (vinyl ether glycerophospholipids) is not completely understood. These lipid species display a propensity for non-lamellar phase formation, facilitating membrane fusion, and modulate the activity of membrane-bound proteins such as enzymes and receptors. At the organism level, plasmalogen deficiency is associated with cardiometabolic disorders including obesity and type 2 diabetes in humans. A straight link is perceived with the susceptibility of such patients to SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) infection, the severity of illness, and the related difficulty in treatment. Based on correlations between the coronavirus-induced modifications of lipid metabolism in host cells, plasmalogen deficiency in the lung surfactant of COVID-19 patients, and the alterations of lipid membrane structural organization and composition including the induction of CM, we emphasize the key role of plasmalogens in the coronavirus (SARS-CoV-2, SARS-CoV, or MERS-CoV) entry and replication in host cells. Considering that plasmalogen-enriched lung surfactant formulations may improve the respiratory process in severe infected individuals, plasmalogens can be suggested as an anti-viral prophylactic, a lipid biomarker in SARS-CoV and SARS-CoV-2 infections, and a potential anti-viral therapeutic component of lung surfactant development for COVID-19 patients.
Highlights
Increasing evidence supports the correlation between diminished levels of plasmalogens and a number of pathological states including neurodegenerative and cardiometabolic disorders as well as the severe acute respiratory distress syndrome due to the coronavirus infections
Dysregulated levels of plasmalogens are found in infected patients as a result of coronavirus-induced modification of the lipid metabolism
Based on the features discussed above, we suggest the potential role of plasmalogen pre-conditioning as anti-viral therapeutic and prophylaxis strategy
Summary
All seven coronaviruses capable of infecting humans, including severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus OC43 (HCoV-OC43), human coronavirus 229E (HCoV-229E), human coronavirus HKU1 (HCoV-HKU1), and human coronavirus NL63 (HCoV-NL63), employ lipid-binding domains for viral entry into host cells, Plasmalogens Role in Coronavirus Infection and Therapy intracellular lipid membrane modifications and host lipid reservoirs for viral replication and proliferation (Knoops et al, 2008; Miller and Krijnse-Locker, 2008; Ulasli et al, 2010; Oudshoorn et al, 2017; Abu-Farha et al, 2020). Tight LA binding can stabilize the locked conformation of the S-protein in SARS-CoV2 coronavirus, which may lead to diminished interaction with host ACE2 receptor Coronavirus infection modifies both lipid composition and membrane structure, topology and trafficking of the host cells in order to ensure virus particle replication and proliferation. Regions of the membrane to interact with hydrophobic domains of peripheral proteins, or (ii) fatty acid moieties of phospholipids to protrude out of the bilayer plane These structural effects can activate anchored enzymes such as PKC and sphingomyelin synthase involved in the lipid metabolism process. Bilayer lipid membranes may rearrange into 3D cubic membranes under stress conditions, which correspond to either altered lipid metabolism or protein overexpression (Almsherqi et al, 2006) in disease states as well as other types of environmental stress including viral infection (Deng et al, 2010), pH changes, presence of ions or solutes of increased concentrations, temperature changes, light, electric field, etc. Such non-lamellar structures are considered as transient states associated with the membrane bending, instabilities and rearrangement caused by the non-lamellar phase transition
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