Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol

Zhang, Yunhang; Song, Zhongbao; Wang, Mi; Lan, Min; Zhang, Kuo; Jiang, Ping; Li, Yufeng; Bai, Juan; Wang, Xianwei

doi:10.1016/j.vetmic.2019.03.004

Cited by 42 publications

(42 citation statements)

References 30 publications

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“…Among the several oxysterols that accumulate in NPC, two are particularly worth highlighting, given their potential relevance to COVID‐19, namely 7‐ketocholesterol (7‐KC) and 25‐hydroxycholesterol (25‐HC) 53 . Both 7‐KC and 25‐HC have been previously reported to possess potent antiviral activities, against various viral families 54‐57 . Specifically, elevated intracellular levels of 25‐HC, have been previously shown to reduce infectivity by several members of the coronaviridae, filoviridae (eg, Ebola virus), and flaviviridae (eg, Zika and hepatitis C viruses) 54‐57 .…”

Section: The Oxysterols That Accumulate In Npc Possess Potent Antivirmentioning

confidence: 99%

“…Both 7‐KC and 25‐HC have been previously reported to possess potent antiviral activities, against various viral families 54‐57 . Specifically, elevated intracellular levels of 25‐HC, have been previously shown to reduce infectivity by several members of the coronaviridae, filoviridae (eg, Ebola virus), and flaviviridae (eg, Zika and hepatitis C viruses) 54‐57 . Similarly, increased intracellular levels of 7‐KC have been shown to interfere with viral maturation, and subsequent budding and release from host cells 58 .…”

Section: The Oxysterols That Accumulate In Npc Possess Potent Antivirmentioning

confidence: 99%

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The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

et al. 2020

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Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID‐19. By describing the life cycle of the newly emergent coronavirus, SARS‐CoV‐2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID‐19. Moreover, we propose that Niemann‐Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS‐CoV‐2, by highlighting key established features of the disorder that together result in an “unfavorable” host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID‐19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC‐like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID‐19.

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Section: The Oxysterols That Accumulate In Npc Possess Potent Antivirmentioning

confidence: 99%

Section: The Oxysterols That Accumulate In Npc Possess Potent Antivirmentioning

confidence: 99%

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

et al. 2020

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“…Also of interest is our finding that BMP regulates oxysterol production, especially 7- and 25-hydroxycholesterol [ 97 , 122 ]. As a matter of fact, these oxysterols have been shown to exert antiviral activity against coronavirus and related virus like Ebola, Zika by decreasing virus entry or replication [ [123] , [124] , [125] ]. This raises the hypothesis of a role of BMP to favor this antiviral activity.…”

Section: Bis(monoacylglycero)phosphate and Cholesterol Homeostasismentioning

confidence: 99%

Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

et al. 2020

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Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19.

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“…Among the various oxysterols that accumulate in NPC, two are worth highlighing in the context of COVID-19. These include 7-ketocholesterol (7KC) and 25-hydroxycholesterol (25-HC) [36], both of which have been shown to possess potent antiviral activities [37][38][39][40]. Increased intracellular 25-HC levels have been shown to reduce infectivity by several members of the coronaviridae, filoviridae (e.g.…”

Section: The Oxysterols That Accumulate In Npc Possess Potent Antivirmentioning

confidence: 99%

“…Increased intracellular 25-HC levels have been shown to reduce infectivity by several members of the coronaviridae, filoviridae (e.g. Ebola virus), and flaviviridae families, including the Zika and hepatitis C viruses [37][38][39][40]. In contrast, elevated intracellular 7-KC levels interfere with viral maturation and subsequent budding and release from host cells [41].…”

Section: The Oxysterols That Accumulate In Npc Possess Potent Antivirmentioning

confidence: 99%

The Lysosome: A Potential Therapeutic Juncture between the COVID-19 Pandemic and Niemann-Pick Type C Disease

Ballout¹

2020

Preprint

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In the face of the newly emergent COVID-19 pandemic, researchers around the world are racing to identify efficacious drugs capable of preventing or treating its infection. They are doing that by testing already available and approved antimicrobials for their rapid repurposing against COVID-19. Using the data emerging on the comparable efficacy of various compounds having different mechanisms of action and indications, I suggest in this report, their potential mechanistic convergence. Specifically, I highlight the lysosome as a key possible therapeutic target for COVID-19, proposing one of the lysosomal storage disorders, Niemann-Pick type C disease (NPC), as a prototypical condition with inherent resistance or an “unfavorable” host cell environment for viral propagation. The included reasoning evolves from previously generated data in NPC, along with the emerging data on COVID-19. The aim of this report is to suggest that pharmacological induction of a “transient” NPC-like lysosomal dysfunction, could hold answers for targeting the ongoing COVID-19 pandemic.

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Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol

Cited by 42 publications

References 30 publications

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

The Lysosome: A Potential Therapeutic Juncture between the COVID-19 Pandemic and Niemann-Pick Type C Disease

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