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A certain proportion of docosahexaenoic acid tends to revert structural and dynamical effects of cholesterol on lipid membranes.
Pedroni, VI, Sierra, MB, Alarcón, LM, Verde, AR, Appignanesi, GA, Morini, MA
Biochimica et biophysica acta. Biomembranes. 2021;(6):183584
Abstract
This work investigates how docosahexaenoic acid (DHA) modifies the effect of Cholesterol (Chol) on the structural and dynamical properties of dipalmitoylphosphatidylcholine (DPPC) membrane. We employ low-cost and non-invasive methods: zeta potential (ZP), conductivity, density, and ultrasound velocity, complemented by molecular dynamics simulations. Our studies reveal that 30% of DHA added to the DPPC-Chol system tends to revert Chol action on a model lipid bilayer. Results obtained in this work shed light on the effect of polyunsaturated fatty acids - particularly DHA - on lipid membranes, with potential preventive applications in many diseases, e.g. neuronal as, Alzheimer's disease, and viral, as Covid-19.
2.
Cholesterol, lipoproteins, and COVID-19: Basic concepts and clinical applications.
Kočar, E, Režen, T, Rozman, D
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2021;(2):158849
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Abstract
Cholesterol is being recognized as a molecule involved in regulating the entry of the SARS-CoV-2 virus into the host cell. However, the data about the possible role of cholesterol carrying lipoproteins and their receptors in relation to infection are scarce and the connection of lipid-associated pathologies with COVID-19 disease is in its infancy. Herein we provide an overview of lipids and lipid metabolism in relation to COVID-19, with special attention on different forms of cholesterol. Cholesterol enriched lipid rafts represent a platform for viruses to enter the host cell by endocytosis. Generally, higher membrane cholesterol coincides with higher efficiency of COVID-19 entry. Inversely, patients with COVID-19 show lowered levels of blood cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins. The modulated efficiency of viral entry can be explained by availability of SR-B1 receptor. HDL seems to have a variety of roles, from being itself a scavenger for viruses, an immune modulator and mediator of viral entry. Due to inverse roles of membrane cholesterol and lipoprotein cholesterol in COVID-19 infected patients, treatment of these patients with cholesterol lowering statins needs more attention. In conclusion, cholesterol and lipoproteins are potential markers for monitoring the viral infection status, while the lipid metabolic pathways and the composition of membranes could be targeted to selectively inhibit the life cycle of the virus as a basis for antiviral therapy.
3.
Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry.
Palacios-Rápalo, SN, De Jesús-González, LA, Cordero-Rivera, CD, Farfan-Morales, CN, Osuna-Ramos, JF, Martínez-Mier, G, Quistián-Galván, J, Muñoz-Pérez, A, Bernal-Dolores, V, Del Ángel, RM, et al
Frontiers in immunology. 2021;:796855
Abstract
Since its appearance, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), the causal agent of Coronavirus Disease 2019 (COVID-19), represents a global problem for human health that involves the host lipid homeostasis. Regarding, lipid rafts are functional membrane microdomains with highly and tightly packed lipid molecules. These regions enriched in sphingolipids and cholesterol recruit and concentrate several receptors and molecules involved in pathogen recognition and cellular signaling. Cholesterol-rich lipid rafts have multiple functions for viral replication; however, their role in SARS-CoV-2 infection remains unclear. In this review, we discussed the novel evidence on the cholesterol-rich lipid rafts as a platform for SARS-CoV-2 entry, where receptors such as the angiotensin-converting enzyme-2 (ACE-2), heparan sulfate proteoglycans (HSPGs), human Toll-like receptors (TLRs), transmembrane serine proteases (TMPRSS), CD-147 and HDL-scavenger receptor B type 1 (SR-B1) are recruited for their interaction with the viral spike protein. FDA-approved drugs such as statins, metformin, hydroxychloroquine, and cyclodextrins (methyl-β-cyclodextrin) can disrupt cholesterol-rich lipid rafts to regulate key molecules in the immune signaling pathways triggered by SARS-CoV-2 infection. Taken together, better knowledge on cholesterol-rich lipid rafts in the SARS-CoV-2-host interactions will provide valuable insights into pathogenesis and the identification of novel therapeutic targets.
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Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review.
Zaki, N, Alashwal, H, Ibrahim, S
Diabetes & metabolic syndrome. 2020;(5):1133-1142
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Abstract
BACKGROUND AND AIMS To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. METHODS A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. Filtering of the articles was then undertaken using keywords and questions, e.g. "Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?". The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. FINDINGS A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. CONCLUSION Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Further research regarding this relationship and its clinical management is warranted.