Inhibitory Activity of Honeysuckle Extracts against Influenza A Virus In Vitro and In Vivo

金银花 奥司他韦 甲型流感病毒 病毒 体内 EC50型 体外 生物 神经氨酸酶 细胞病变效应 化学 植物化学 神经氨酸酶抑制剂 微生物学 药理学 病毒学 生物化学 医学 传染病(医学专业) 替代医学 中医药 生物技术 疾病 病理 2019年冠状病毒病(COVID-19)
作者
Mengwei Li,Yuxu Wang,Jing Jin,Jie Dou,Qinglong Guo,Xue Ke,Changlin Zhou,Min Guo
出处
期刊:Virologica Sinica [Springer Nature]
卷期号:36 (3): 490-500 被引量:34
标识
DOI:10.1007/s12250-020-00302-6
摘要

Honeysuckle has been used in the treatment of influenza virus infection for thousands of years in China. However, its main active components and the functional mechanisms remain to be elucidated. Here, four honeysuckle extracts, including acids extract, flavonoids extract, total extract and acids-flavonoids mixture, were prepared to clarify the main active antiviral components. The cytopathic effect reduction assay showed that all the four extracts inhibited the replication of influenza viruses H1N1, H3N2 and the oseltamivir-resistant mutant strain H1N1-H275Y. The acids-flavonoids mixture had the strongest inhibitory effects in vitro with EC50 values of 3.8, 4.1, and > 20 μg/mL against H1N1, H3N2 and H1N1-H275Y, respectively, showing competitive antiviral activity with oseltamivir and ribavirin. Honeysuckle acids extract also showed the most significant antiviral activity in vivo. Oral administration of the acids extract at a dosage of 600 mg/kg/d effectively alleviated viral pneumonia, maintained body weight and improved the survival rate to 30% of the mice infected with a lethal dose of H1N1. The results of time-of-drug addition experiment and neuraminidase (NA) inhibition assay showed that honeysuckle extracts had a broad-spectrum inhibitory effect against influenza virus NAs. The flavonoid extract showed the strongest inhibitory effect on the NA of influenza virus H7N9 with an IC50 of 24.7 μg/mL. These results suggested that these extracts might exert their antiviral activity by suppressing the release of influenza viruses. Briefly, our findings demonstrate that acids and flavonoids extracts of honeysuckle are the major antiviral active components, and the acids extract has the potential to be developed into an antiviral agent against influenza virus, especially for oseltamivir-resistant viruses.
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