Targeting host lipid flows: Exploring new antiviral and antibiotic strategies

Fernández-Oliva, Alberto; Ortega-González, Paula; Risco, Cristina

doi:10.1111/cmi.12996

Cited by 29 publications

(29 citation statements)

References 204 publications

(288 reference statements)

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“…In the viral context, viruses could subvert cholesterol homoeostasis generating a protective membrane environment that facilitates virus assembly and proliferation (Deng, Almsherqi, Ng, & Kohlwein, 2010). Therefore, some authors propose targeting host cell lipid flux as a potential new antibacterial and antiviral strategy (Fernandez‐Oliva, Ortega‐Gonzalez, & Risco, 2019). Accordingly, the use of methyl‐β‐cyclodextrin for cholesterol depletion and lipid raft disruption decreased the infectivity of several viruses, such as HCV or bovine parainfluenza virus, mainly through blocking virus entry into host cells (Fernandez‐Oliva et al, 2019).…”

Section: Statins Modulate Lipid Rafts: Potential Role In Sars‐cov‐2 Imentioning

confidence: 99%

“…Therefore, some authors propose targeting host cell lipid flux as a potential new antibacterial and antiviral strategy (Fernandez‐Oliva, Ortega‐Gonzalez, & Risco, 2019). Accordingly, the use of methyl‐β‐cyclodextrin for cholesterol depletion and lipid raft disruption decreased the infectivity of several viruses, such as HCV or bovine parainfluenza virus, mainly through blocking virus entry into host cells (Fernandez‐Oliva et al, 2019). Similar results were observed using gemfibrozil as a lipid‐lowering drug (Bajimaya et al, 2017).…”

Section: Statins Modulate Lipid Rafts: Potential Role In Sars‐cov‐2 Imentioning

confidence: 99%

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Statins: Could an old friend help in the fight against COVID‐19?

Rodrigues-Díez

Tejera‐Muñoz

Márquez‐Expósito

et al. 2020

British J Pharmacology

114

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The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomes.

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Section: Statins Modulate Lipid Rafts: Potential Role In Sars‐cov‐2 Imentioning

confidence: 99%

Section: Statins Modulate Lipid Rafts: Potential Role In Sars‐cov‐2 Imentioning

confidence: 99%

Statins: Could an old friend help in the fight against COVID‐19?

Rodrigues-Díez

Tejera‐Muñoz

Márquez‐Expósito

et al. 2020

British J Pharmacology

114

View full text Add to dashboard Cite

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“…Even though it is not one of their constituents, pathogenesis by some intracellular bacteria requires cellular cholesterol. Both innate cellular defenses and therapeutic remedies exploit this sterol dependence to combat such infections 63 . It was shown recently that cells reduce their susceptibility to certain bacteria and toxins by downregulating active plasma membrane cholesterol 64,65 …”

Section: Active Cholesterolmentioning

confidence: 99%

Active cholesterol 20 years on

Lange

Steck

2020

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This review considers the following hypotheses, some well‐supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with bilayer phospholipids in complexes of varied strength and stoichiometry. These complexes underlie many of the material properties of the bilayer. The small fraction of cholesterol molecules exceeding the binding capacity of the phospholipids is thermodynamically active and serves diverse functions. It circulates briskly among the cell membranes, particularly through contact sites linking the organelles. Active cholesterol provides the upstream feedback signal to multiple mechanisms governing plasma membrane homeostasis, pegging the sterol level to a threshold set by its phospholipids. Active cholesterol could also be the cargo for various inter‐organelle transporters and the form excreted from cells by reverse transport. Furthermore, it is integral to the function of caveolae; a mediator of Hedgehog regulation; and a ligand for the binding of cytolytic toxins to membranes. Active cholesterol modulates a variety of plasma membrane proteins—receptors, channels and transporters—at least in vitro.

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“…Inflammatory cytokines stimulate the formation of 25-HC, which in turn, promotes adipose tissue inflammation that is found in diabetes and obesity (121). The targeting of cholesterol and lipid metabolism and distribution has been proposed as a novel strategy for treating viral infections (122). The need for clustering of ACE2 and TMPRSS2 within organized domains in lipid rafts for viral entry could help explain some of the seemingly discrepant reports that increased ACE2 could facilitate infection, as described above, or actually protect against infection (123).…”

Section: Lipid Raftsmentioning

confidence: 99%

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

et al. 2020

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The pandemic of COVID-19, caused by the coronavirus, SARS-CoV-2, has had a global impact not seen for an infectious disease for over a century. This acute pandemic has spread from the East and has been overlaid onto a slow pandemic of metabolic diseases of obesity and diabetes consequent from the increasing adoption of a Western-lifestyle characterized by excess calorie consumption with limited physical activity. It has become clear that these conditions predispose individuals to a more severe COVID-19 with increased morbidity and mortality. There are many features of diabetes and obesity that may accentuate the clinical response to SARS-CoV-2 infection: including an impaired immune response, an atherothrombotic state, accumulation of advanced glycation end products and a chronic inflammatory state. These could prime an exaggerated cytokine response to viral infection, predisposing to the cytokine storm that triggers progression to septic shock, acute respiratory distress syndrome, and multi-organ failure. Infection leads to an inflammatory response and tissue damage resulting in increased metabolic activity and an associated increase in the mechanisms by which cells ingest and degrade tissue debris and foreign materials. It is becoming clear that viruses have acquired an ability to exploit these mechanisms to invade cells and facilitate their own life-cycle. In obesity and diabetes these mechanisms are chronically activated due to the deteriorating metabolic state and this may provide an increased opportunity for a more profound and sustained viral infection.

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Targeting host lipid flows: Exploring new antiviral and antibiotic strategies

Cited by 29 publications

References 204 publications

Statins: Could an old friend help in the fight against COVID‐19?

Statins: Could an old friend help in the fight against COVID‐19?

Active cholesterol 20 years on

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

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