Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a Mouse Model of Allergic Airway Inflammation

Abou-Hamdan, Mhamad; Gharib, Bouchra; Bajénoff, Marc; Julia, Valérie; Reggi, Max de

doi:10.12659/msmbr.904077

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Pantethine could also exert its effects during subsequent stages of the SARS-CoV-2 replication cycle, for example, by disturbing intracellular mechanisms dependent on cholesterol or thiol-disulfide homeostasis or altering viral egression via inhibition of infection-induced HECT E3 ligase expression. Pantethine also presents additional nonlipid-related pleiotropic effects, such as anti-inflammatory, antioxidant, and anticoagulant effects 4 , 6 , 29 , 30 , 70 , that might confer benefits in patients with severe COVID-19 and long COVID syndrome. As it has already been used in humans with no significant adverse effects, pantethine displays a variety of mechanisms and functions that make it a potential tool for antiviral therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Potential antiviral effects of pantethine against SARS-CoV-2

Abou-Hamdan

Saleh

Mani

et al. 2023

Sci Rep

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SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection, in Vero E6 cells and in Calu-3a cells. Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome.

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Section: Discussionmentioning

confidence: 99%

Potential antiviral effects of pantethine against SARS-CoV-2

Abou-Hamdan

Saleh

Mani

et al. 2023

Sci Rep

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show abstract

“…Pantethine also presents additional nonlipid-related pleiotropic effects, such as antiinflammatory, antioxidant, and anticoagulant effects 4,6,[65][66][67] , that might confer benefits in patients with severe COVID-19 and long COVID syndrome. As it has already been used in humans with no significant adverse effects, pantethine displays a variety of mechanisms and functions that make it a potential tool for antiviral therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Potential antiviral effects of pantethine against SARS-CoV-2

Abou-Hamdan

Saleh

Mani

et al. 2022

Preprint

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SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection.Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome.

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“…Allergic diseases are experienced worldwide, with various risk factors and triggers that occur according to geographical and environmental differences ( 1 ). Allergic asthma is a heterogeneous inflammatory lung disease, characterized by lung inflammation, airway hyperresponsiveness (AHR) and airway remodeling ( 2 ). Statistically, ~300 million individuals worldwide suffer from asthma ( 3 ), half of which are allergic, with the incidence continuously increasing.…”

Section: Introductionmentioning

confidence: 99%

Environmental allergens house dust mite‑induced asthma is associated with ferroptosis in the lungs

Tang

Dong²,

Teng

et al. 2021

Exp Ther Med

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Previous studies have indicated that allergens such as house dust mites (HDM) in the environment can induce allergic asthma. Ferroptosis is a newly discovered form of regulatory cell death characterized by aberrant lipid peroxidation and the accumulation of reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological process of asthma remains to be elucidated. The present study used a HDM-induced mouse asthma model to determine the effect of HDM exposure on allergic asthma and its underlying mechanisms. Female BALB/c mice were intranasally exposed to HDM to induce allergic asthma. Airway hyperresponsiveness (AHR), lung inflammation, mucus secretion, IgE levels, cytokine levels and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mitochondria, ROS levels, glutathione (GSH) levels and changes in ferroptosis pathway proteins were also determined in murine lungs. As a result, HDM exposure significantly increased AHR, inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated IgE levels in the BALF, lung eosinophilia and a concomitant increase in IL-13 and IL-5 levels in BALF were observed. HDM inhalation increased ROS and decreased GSH levels in the lungs. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blotting demonstrated that the activities of glutathione peroxidase 4 and catalytic subunit solute carrier family 7 member 11 were significantly decreased, and that protein expression levels of acyl-CoA synthetase long-chain family member 4 and 15 lipoxygenase 1 were upregulated compared with mice in the normal control group. Overall, these results indicated that the AHR, airway inflammation, lipid peroxidation and ROS levels increased in HDM-induced asthma, and that HDM inhalation induced ferroptosis in the lungs, which helped to form an improved understanding of the pathogenesis of allergic asthma.

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Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a Mouse Model of Allergic Airway Inflammation

Cited by 4 publications

References 21 publications

Potential antiviral effects of pantethine against SARS-CoV-2

Potential antiviral effects of pantethine against SARS-CoV-2

Potential antiviral effects of pantethine against SARS-CoV-2

Environmental allergens house dust mite‑induced asthma is associated with ferroptosis in the lungs

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