Anti-flavivirus Properties of Lipid-Lowering Drugs

Farfán-Morales, Carlos Noe; Cordero-Rivera, Carlos Daniel; Reyes-Ruiz, José Manuel; Hurtado-Monzón, Arianna Mahely; Osuna-Ramos, Juan Fidel; González-González, Arely M.; Jesús-González, Luis Adrián De; Palacios-Rápalo, Selvin Noé; Ángel, Rosa M. del

doi:10.3389/fphys.2021.749770

Cited by 21 publications

(11 citation statements)

References 277 publications

(405 reference statements)

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“…Some FDA-approved cholesterol-lowering drugs have antiviral properties and are safe for use in humans, which reduces the time and requirements for their study in clinical trials (179). In this regard, statins and metformin are promising candidates for the treatment of infections caused by enveloped viruses, such as Dengue virus (DENV), Zika virus (ZIKV), hepatitis C virus (HCV), Japanese encephalitis virus (JEV), influenza A virus (IAV), and recently for the treatment of SARS-CoV-2 (180)(181)(182)(183)(184). These drugs interfere in different metabolic pathways for lipid synthesis by inhibiting critical cholesterol and fatty acid synthesis (185).…”

Section: Targeting Cholesterol-rich Lipid Rafts As Potential Therapeutics In Sars-cov-2 Infectionmentioning

confidence: 99%

“…It should be noted that their use as antivirals suggests an acute and short-term treatment, reducing the side effects associated with long periods of treatment (209,(211)(212)(213). Preclinical studies are necessary to evaluate its safety during viral infections, as currently metformin is evaluated during ZIKV infections (184,214,215).…”

Section: Targeting Cholesterol-rich Lipid Rafts As Potential Therapeutics In Sars-cov-2 Infectionmentioning

confidence: 99%

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Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry

et al. 2021

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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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Section: Targeting Cholesterol-rich Lipid Rafts As Potential Therapeutics In Sars-cov-2 Infectionmentioning

confidence: 99%

Section: Targeting Cholesterol-rich Lipid Rafts As Potential Therapeutics In Sars-cov-2 Infectionmentioning

confidence: 99%

Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry

et al. 2021

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“…JEV in one of enveloped RNA viruses which can caused human severe central system infection diseases,the life cycle of this viruses is critically dependent on host lipid biosynthesis [22] ,pivotal biological function of lipid metabolism during JEV infection [23] .From viral binding and entry,infection by these viruses leads to reorganization of cellular membranes and lipid metabolism to support the production of new viral particles [24,25] . Recent work has focused on de ning the involvement of speci c lipid classes in above process in hopes of identifying potential therapeutic targets for the treatment or prevention of disease.…”

Section: Discussionmentioning

confidence: 99%

Japanese Encephalitis Virus-Induced Peripheral Neuropathy in the Rat Model

Zhang

Yuan

Yang

et al. 2022

Preprint

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Background: Guillain–Barré Syndrome Associated with Japanese encephalitis virus(JEV) infection,the mechanism of JEV which caused peripheral nerve injury remains unknown.Recently, it has been suggested that an altered sphingolipid metabolism may contribute to the pathogenesis of peripheral neuropathy. In light of the emerging evidence of peripheral nerve injury when JEV infected and the evidence in the pathogenesis of neuroimmunity, we aimed to make a rat model which peripheral nerve injury after JEV infection and investigate relevant damage mechanism. Methods: We investigated the infected rat with peripheral neuropathy induced by JEV. The rat exhibited behavioral and pathological signs of peripheral nervous injury. The motor function of rats were determined by clinical scoring and tissue examination.Electrophysiological measurements and transmission electron microscopy was used on sciatic nerves to assess peripheral peripheral nervous injury.ELISA were used to evaluate IFNγ, IL-17,ceramide and acid sphingomyelinase level. Immunofluorescence was performed on sciatic nerves to assess the expression and localization of ceramide and matrix metalloproteinase-9.Results: Japanese encephalitis virus induced peripheral neuropathy in rat,evidenced by the aggravated clinical scores, electrophysiological,transmission electron microscopy,circulating pro-inflammatory cytokines, and histological anomalies, suggesting that demyelination and axonal damage of sciatic nerves. JEV destroyed the tight junction structure of rat’s blood nerve barrier and increased ceramide and matrix metalloproteinase-9.Conclusion:These data suggest that JEV is a potential reason caused peripheral nerve injury in rat model and this model can be used for the investigation of the roles of various cytokines and acid sphingomyelinase,ceramide system in infection-induced peripheral neuropathy. Further investigation of this model could give a better understanding and lead to more effective evidences for JEV infection-associated peripheral neuropathy.

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“…As HBV and HCV often cause chronic hepatitis, research scientists have developed (are developing) strategies to deal with their infections. As discussed previously, lipid and cholesterol metabolism and homeostasis are crucial for hepatitis viral infection; cholesterol/lipid metabolism have been identified as potential antiviral targets [ 90 ]. Indeed, cellular cholesterol has been identified as a critical factor in a variety of viral infections [ 91 , 92 , 93 , 94 , 95 , 96 ].…”

Section: Therapeutic Potential Of Natural Phytochemicals Targeting Ch...mentioning

confidence: 99%

Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds

Liou

Mani

Yen

2022

IJMS

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Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in liver fibrosis, cirrhosis, and sometimes liver failure or cancer. Hepatitis is often caused by viral infections. The most common causes of viral hepatitis are the five hepatitis viruses—hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). While HAV and HEV rarely (or do not) cause chronic hepatitis, a considerable proportion of acute hepatitis cases caused by HBV (sometimes co-infected with HDV) and HCV infections become chronic. Thus, many medical researchers have focused on the treatment of HBV and HCV. It has been documented that host lipid metabolism, particularly cholesterol metabolism, is required for the hepatitis viral infection and life cycle. Thus, manipulating host cholesterol metabolism-related genes and proteins is a strategy used in fighting the viral infections. Efforts have been made to evaluate the efficacy of cholesterol-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the treatment of hepatitis viral infections; promising results have been obtained. This review provides information on the relationships between hepatitis viruses and host cholesterol metabolism/homeostasis, as well as the discovery/development of cholesterol-lowering natural phytochemicals that could potentially be applied in the treatment of viral hepatitis.

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Anti-flavivirus Properties of Lipid-Lowering Drugs

Cited by 21 publications

References 277 publications

Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry

Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry

Japanese Encephalitis Virus-Induced Peripheral Neuropathy in the Rat Model

Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds

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