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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

Natural compound ailanthone alleviates herpes simplex keratitis in mice by inhibiting HSV-1 replication

6 affiliations
  1. 1Anhui Key Laboratory of Infection and Immunity, School of Basic Medicine, Bengbu Medical University
  2. 2Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University
  3. 3Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University
  4. 4School of Stomatology, Nanchang University
  5. 5Department of Ophthalmology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
  6. 6School of Pharmacy, Nanjing University of Chinese Medicine

Abstract

Background: Herpes simplex keratitis (HSK), caused by herpes simplex virus type I (HSV-1) infection, is a common ocular disease that can lead to corneal scarring and visual impairment. Since current antiviral drugs exhibit limited efficacy against HSK, it is necessary to explore new therapeutic strategies for the treatment of HSV-1 infection-related diseases.

Purpose: This study aimed to explore the potential role of ailanthone, a plant-derived natural compound, as a therapeutic drug for reducing HSV-1 replication and alleviating the progression of HSK.

Methods: A library of natural compounds was screened and in vitro assays were performed to examine the inhibition of HSV-1 replication by ailanthone; Network pharmacology analysis and molecular docking prioritized integrin beta 2 (ITGB2) as a potential functional target of ailanthone. In vivo assays conducted to evaluate the anti-viral activity of ailanthone using an HSK mouse model.

Results: The study discovered that ailanthone is a potent HSV-1 inhibitor identified by screening. It suppressed viral gene expression and viral titers in vitro by downregulating ITGB2, a host factor supporting viral replication. Furthermore, ailanthone treatment at a low dose (1 mg/kg) and a high dose (5 mg/kg) significantly alleviated corneal lesions and reduced the corneal viral load in a mouse model of HSK.

Conclusion: In conclusion, this study provided evidence that ITGB2 supported HSV-1 replication and identified a plant-derived natural compound, ailanthone, which suppresses HSV-1 replication via modulating ITGB2 expression, providing a potential drug candidate and therapeutic target for HSK treatment.

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BibTeX
@article{chen2026natural,
  title = {{Natural compound ailanthone alleviates herpes simplex keratitis in mice by inhibiting HSV-1 replication}},
  author = {Li Chen and Enhui Yang and Xinyue Zhang and Le Zhang and Lei Wu and Shiqi Chen and Wei Jin and Qin Qin and Rui Chen and Jing Wu and Deyan Chen},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1937590},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1937590/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Natural compound ailanthone alleviates herpes simplex keratitis in mice by inhibiting HSV-1 replication
AU  - Li Chen
AU  - Enhui Yang
AU  - Xinyue Zhang
AU  - Le Zhang
AU  - Lei Wu
AU  - Shiqi Chen
AU  - Wei Jin
AU  - Qin Qin
AU  - Rui Chen
AU  - Jing Wu
AU  - Deyan Chen
PY  - 2026
DA  - 2026/10/21
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1937590
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1937590/full
AB  - Background: Herpes simplex keratitis (HSK), caused by herpes simplex virus type I (HSV-1) infection, is a common ocular disease that can lead to corneal scarring and visual impairment. Since current antiviral drugs exhibit limited efficacy against HSK, it is necessary to explore new therapeutic strategies for the treatment of HSV-1 infection-related diseases.  Purpose: This study aimed to explore the potential role of ailanthone, a plant-derived natural compound, as a therapeutic drug for reducing HSV-1 replication and alleviating the progression of HSK.  Methods: A library of natural compounds was screened and in vitro assays were performed to examine the inhibition of HSV-1 replication by ailanthone; Network pharmacology analysis and molecular docking prioritized integrin beta 2 (ITGB2) as a potential functional target of ailanthone. In vivo assays conducted to evaluate the anti-viral activity of ailanthone using an HSK mouse model.  Results: The study discovered that ailanthone is a potent HSV-1 inhibitor identified by screening. It suppressed viral gene expression and viral titers in vitro by downregulating ITGB2, a host factor supporting viral replication. Furthermore, ailanthone treatment at a low dose (1 mg/kg) and a high dose (5 mg/kg) significantly alleviated corneal lesions and reduced the corneal viral load in a mouse model of HSK.  Conclusion: In conclusion, this study provided evidence that ITGB2 supported HSV-1 replication and identified a plant-derived natural compound, ailanthone, which suppresses HSV-1 replication via modulating ITGB2 expression, providing a potential drug candidate and therapeutic target for HSK treatment.
SN  - 1663-9812
ER  -