Inhibitory effects of baicalein against herpes simplex virus type 1

• Published in: Acta pharmaceutica Sinica. B 2020-12, Vol.10 (12), p.2323-2338
• Main Authors: Luo, Zhuo, Kuang, Xiu-Ping, Zhou, Qing-Qing, Yan, Chang-Yu, Li, Wen, Gong, Hai-Biao, Kurihara, Hiroshi, Li, Wei-Xi, Li, Yi-Fang, He, Rong-Rong
• Format: Article
• Language: English
• Subjects: Anti-HSV-1; Baicalein; HSV-1 infection; IKK-β phosphorylation; NF-κB activation; Original; Viral inactivation
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2020.06.008

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. [Display omitted] Baicalein exerts potent ability against HSV-1 infection and dual mechanisms were disclosed. •Baicalein is highly effective against HSV-1infection ex vivo and in vivo.•Inactivation of viral particles and suppression of NF-κB 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.