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

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.

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.

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.

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.

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.