Inhibitory effects of baicalein against herpes simplex virus type 1

ABSTRACT: 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 I?B kinase beta (IKK-?) 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. Graphical abstract Image 1Baicalein exerts potent ability against HSV-1 infection and dual mechanisms were disclosed. Highlights • Baicalein is highly effective against HSV-1infection ex vivo and in vivo.• Inactivation of viral particles and suppression of NF-?B activation were involved in the anti-viral effect of baicalein.• Hence, our work offers experimental basis for baicalein as a potential drug in treating HSV-1 associated diseases.

SUBMITTER: Luo Z 

PROVIDER: S-EPMC7745058 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature