目的 基于绵马贯众中间苯三酚类成分寻找具有良好抗流感病毒活性的化合物。方法 将25个绵马贯众中间苯三酚类化合物与12种流感病毒神经氨酸酶（neuraminidase，NA）进行分子对接，通过评价结合能、结合模式及发生相互作用的重要氨基酸等指标进行虚拟筛选。通过神经氨酸酶抑制实验验证其中4个候选化合物体外抑制NA的活性，在此基础上，采用犬肾MDCK细胞通过细胞病变（CPE）法对候选化合物M22的抗病毒活性进行进一步的验证。结果 通过分子对接筛选出5个与NA有较好结合能力的候选化合物；NA抑制实验结果表明候选化合物中M22对NA抑制作用最显著；CPE实验结果表明M22对多种流感病毒毒株均具有较好的抑制作用。结论 绵马贯众中候选化合物M22具有较好的抗流感病毒作用，为开发新的抗流感病毒药物的深入研究奠定了基础。

Objective To find the most active phloroglucinol compound on influenza virus from Dryopteris crassirhizoma. Methods Twenty-five phloroglucinols from D. crassirhizoma were docked into 12 kinds neuraminidase (NA) for molecular docking. The binding energies, the combination of compound and neuraminidase and the interaction with the important amino acid residues were used for virtual screening. The inhibitory effect in vitro of four candidate compounds on NA was tested by NA inhibition assay, on this basis, M22 was evaluated for its antiviral activity on MDCK cells via CPE assay. Results Virtual screening suggested that five candidates had strong binding abilities with NA. NA inhibition assay showed that M22 have the strongest activity against NA of all candidates. CPE assays demonstrated that M22 exhibited inhibitory activity on various influenza virus. Conclusion M22 from D. crassirhizoma have significant inhibitory efficacy on influenza virus. The results provide us with useful information for the development of novel anti-influenza drugs.

国家自然科学基金面上项目（31270400）