Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including
cold sores, corneal
blindness, and
encephalitis. Currently, the use of
nucleoside analogs, such as
acyclovir and
penciclovir, in treating HSV-1
infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that
baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models.
Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an
acyclovir-resistant strain) in vitro. In the ocular inoculation mice model,
baicalein markedly reduced in vivo HSV-1/F replication, receded inflammatory storm and attenuated histological changes in the cornea. Consistently,
baicalein was found to reduce the mortality of mice, viral loads both in nose and trigeminal ganglia in HSV-1 intranasal
infection model. Moreover, an ex vivo HSV-1-EGFP
infection model established in isolated murine epidermal sheets confirmed that
baicalein suppressed HSV-1 replication. Further investigations unraveled that dual mechanisms, inactivating viral particles and inhibiting IκB
kinase beta (IKK-β) phosphorylation, were involved in the anti-HSV-1 effect of
baicalein. Collectively, our findings identified
baicalein as a promising
therapy candidate against the
infection of HSV-1, especially
acyclovir-resistant strain.