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Magnolol against enterovirus 71 by targeting Nrf2-SLC7A11-GSH pathway
Dingran Zhao1, Xueyang Guo1, Binbin Lin2
1State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430072, China.
Abstract:
Enterovirus 71 (EV71), a prominent pathogen associated with hand, foot, and mouth disease (HFMD), has been reported worldwide. To date, the advancement of effective drugs targeting EV71 remains in the preliminary experimental stage. In this study, magnolol demonstrated a significant dose-dependent inhibition of EV71 replication in vitro. It upregulated the overall expression level of nuclear factor erythroid 2 - related factor 2 (Nrf2) and facilitated its nucleus translocation, resulting in the increased expression of various ferroptosis inhibitory genes. This process led to a reduction in reactive oxygen species (ROS) accumulation induced by viral infection. Additionally, magnolol exhibited a broad-spectrum antiviral effect against enteroviruses. Notably, treatment with magnolol substantially enhanced the survival rate of EV71-infected mice, attenuated viral load in heart, liver, brain, and limb tissues, and mitigated tissue inflammation. Taken together, magnolol emerges as a promising candidate for the development of anti-EV71 drugs.
Insights
Magnolol effectively inhibits Enterovirus 71 (EV71) replication by boosting Nrf2 activity and reducing oxidative stress. This natural compound shows promise as a potential therapeutic for hand, foot, and mouth disease (HFMD).
Area of Science:
- Virology
- Pharmacology
- Immunology
Background:
- Enterovirus 71 (EV71) is a significant cause of hand, foot, and mouth disease (HFMD) globally.
- Current therapeutic options for EV71 infections are limited and in early experimental stages.
Purpose of the Study:
- To investigate the antiviral potential of magnolol against EV71.
- To elucidate the underlying molecular mechanisms of magnolol's antiviral activity.
Main Methods:
- In vitro assays to assess EV71 replication inhibition by magnolol.
- Analysis of nuclear factor erythroid 2 - related factor 2 (Nrf2) pathway activation.
- In vivo studies using EV71-infected mouse models.
Main Results:
- Magnolol demonstrated significant, dose-dependent inhibition of EV71 replication in vitro.
- Magnolol upregulated Nrf2 expression and nuclear translocation, increasing ferroptosis inhibitors and reducing reactive oxygen species (ROS).
- Magnolol treatment improved survival rates in infected mice, reduced viral loads, and mitigated tissue inflammation.
Conclusions:
- Magnolol exhibits broad-spectrum antiviral activity against enteroviruses, including EV71.
- Magnolol represents a promising therapeutic candidate for developing novel anti-EV71 drugs.
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