The Fatty Acid Lipid Metabolism Nexus in COVID-19

Tanner, Jerome E.; Alfieri, Caroline

doi:10.3390/v13010090

Cited by 64 publications

(84 citation statements)

References 147 publications

(180 reference statements)

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“…It is very well known that virus ramps up the fatty acid synthesis to support its growth i.e. synthesis of viral membranes [43]. For all the reactions in the fatty acid biosynthesis pathways, we see a high flux through them.…”

Section: Plos Computational Biologymentioning

confidence: 91%

Genome Scale-Differential Flux Analysis reveals deregulation of lung cell metabolism on SARS-CoV-2 infection

Nanda

Ghosh

2021

PLoS Comput Biol

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The COVID-19 pandemic is posing an unprecedented threat to the whole world. In this regard, it is absolutely imperative to understand the mechanism of metabolic reprogramming of host human cells by SARS-CoV-2. A better understanding of the metabolic alterations would aid in design of better therapeutics to deal with COVID-19 pandemic. We developed an integrated genome-scale metabolic model of normal human bronchial epithelial cells (NHBE) infected with SARS-CoV-2 using gene-expression and macromolecular make-up of the virus. The reconstructed model predicts growth rates of the virus in high agreement with the experimental measured values. Furthermore, we report a method for conducting genome-scale differential flux analysis (GS-DFA) in context-specific metabolic models. We apply the method to the context-specific model and identify severely affected metabolic modules predominantly comprising of lipid metabolism. We conduct an integrated analysis of the flux-altered reactions, host-virus protein-protein interaction network and phospho-proteomics data to understand the mechanism of flux alteration in host cells. We show that several enzymes driving the altered reactions inferred by our method to be directly interacting with viral proteins and also undergoing differential phosphorylation under diseased state. In case of SARS-CoV-2 infection, lipid metabolism particularly fatty acid oxidation, cholesterol biosynthesis and beta-oxidation cycle along with arachidonic acid metabolism are predicted to be most affected which confirms with clinical metabolomics studies. GS-DFA can be applied to existing repertoire of high-throughput proteomic or transcriptomic data in diseased condition to understand metabolic deregulation at the level of flux.

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Section: Plos Computational Biologymentioning

confidence: 91%

Genome Scale-Differential Flux Analysis reveals deregulation of lung cell metabolism on SARS-CoV-2 infection

Nanda

Ghosh

2021

PLoS Comput Biol

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“…Researchers have investigated the beneficial use of treating COVID-19 using metformin, a biguanide derivative used to treat type 2 diabetes mellitus (T2DM), due to its antiviral and anti-inflammatory properties [ 171 ]. Studies have suggested that metformin activates the AMPK cascade by forming v-ATPase/Ragulator complex, which is associated with LKB1 and axis inhibition protein 1 (AXIN1), thus leading to AMPK activation and inhibition of mTORC1 [ 172 , 173 ]. Other suggested mechanisms of metformin inhibition of SARS-CoV-2 may occur with respect to its interaction with angiotensin converting enzyme 2 receptor (ACE2) following the activation of AMPK.…”

Section: Ampk and Covid-19mentioning

confidence: 99%

“…Metformin may enhance the phosphorylation of ACE2, leading to a conformational change and decrease binding and entry of SARS-CoV-2 [ 174 , 175 ]. Other mechanisms of metformin action are through AMPK-dependent reduction in lipid storage, increased fatty acid oxidation, and inhibition of glycolysis and lipogenesis [ 172 ]. SARS-CoV-2 was reported to increase the production of lipid anabolic enzymes including fatty acid synthase (FASN), a key regulator in palmitate synthesis and acetyl-CoA carboxylase (ACC1), which plays a key role in palmitoylation of proteins by increasing the activity of the PI3K/AKT/mTOR/S6K signaling pathway [ 172 , 176 ].…”

Section: Ampk and Covid-19mentioning

confidence: 99%

“…Other mechanisms of metformin action are through AMPK-dependent reduction in lipid storage, increased fatty acid oxidation, and inhibition of glycolysis and lipogenesis [ 172 ]. SARS-CoV-2 was reported to increase the production of lipid anabolic enzymes including fatty acid synthase (FASN), a key regulator in palmitate synthesis and acetyl-CoA carboxylase (ACC1), which plays a key role in palmitoylation of proteins by increasing the activity of the PI3K/AKT/mTOR/S6K signaling pathway [ 172 , 176 ]. Activated AMPK blocks fatty acid synthesis directly by inhibiting ACC1, or indirectly by decreasing cellular FASN and ACC1 enzymes via inhibition of mTORC1, or by inhibiting sterol regulatory-element binding protein-1 (SREBP-1) translocation and maturation in the Golgi body, thus preventing lipid gene transcription [ 172 ].…”

Section: Ampk and Covid-19mentioning

confidence: 99%

“…Another repurposed treatment to combat SARS-CoV-2 is orlistat, an inhibitor of FASN, commonly prescribed for the treatment of obesity and obesity-related T2DM. Direct inhibition of FASN activity impairs production of palmitate, thereby inhibiting viral protein palmitoylation [ 172 ]. Orlistat was also proposed to inhibit VPS34, a phosphoinositide kinase that functions in autophagy, endosomal trafficking, and other cellular functions [ 177 ].…”

Section: Ampk and Covid-19mentioning

confidence: 99%

See 2 more Smart Citations

Multifaceted Role of AMPK in Viral Infections

Bhutta

Gallo²,

Borenstein

2021

Cells

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Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5′-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/threonine kinase, plays a significant role in the modulation of infection. Traditionally, AMPK is a key energy regulator of cell growth and proliferation, host autophagy, stress responses, metabolic reprogramming, mitochondrial homeostasis, fatty acid β-oxidation and host immune function. In this review, we highlight the modulation of host AMPK by various viruses under physiological conditions. These intracellular pathogens trigger metabolic changes altering AMPK signaling activity that then facilitates or inhibits viral replication. Considering the COVID-19 pandemic, understanding the regulation of AMPK signaling following infection can shed light on the development of more effective therapeutic strategies against viral infectious diseases.

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Exploration of the link between COVID‐19 and alcoholic hepatitis from the perspective of bioinformatics and systems biology

Huang

Zhou

et al. 2023

MedComm – Future Medicine

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been suggested to purpose threats to health of mankind. Alcoholic hepatitis (AH) is a life-threatening acute and chronic liver failure that takes place in sufferers who drink excessively. During the epidemic, AH has an increasing incidence of severe illness and mortality. The intrinsic relationship of molecular pathogenesis, as well as common therapeutic strategies for two diseases are still poorly understood. The transcriptome of the COVID-19 and AH has been compared to obtain the altered genes and hub genes were screened out through protein-protein interaction (PPI) network analysis.Via gene ontology (GO), pathway enrichment, and transcription regulator analysis, a deeper appreciation of the interplay mechanism between hub genes were established. Finally, gene-disease and gene-drug analysis were displayed to instruct the clinical treatments. With 181 common differentially expressed genes (DEGs) of AH and COVID-19 were obtained, 10 hub genes were captured. Follow-up studies located that these 10 genes typically mediated the diseases occurrence by regulating the activities of the immune system. Other results suggest that the common pathways of the two ailments are enriched in regulating the function of immune cells and release of immune molecules. The top 10 drug candidates have been chosen primarily, some of which have been proved effective in treating AH sufferers infected with COVID-19. This study reveals the common pathogenesis of COVID-19 and AH and assist to discover necessary therapeutic targets to combat the ongoing pandemic induced via MedComm -Future Medicine.

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The Fatty Acid Lipid Metabolism Nexus in COVID-19

Cited by 64 publications

References 147 publications

Genome Scale-Differential Flux Analysis reveals deregulation of lung cell metabolism on SARS-CoV-2 infection

Genome Scale-Differential Flux Analysis reveals deregulation of lung cell metabolism on SARS-CoV-2 infection

Multifaceted Role of AMPK in Viral Infections

Exploration of the link between COVID‐19 and alcoholic hepatitis from the perspective of bioinformatics and systems biology

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