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地锦叶提取物对甲型流感病毒A/PR/8/34(H1N1)的细胞毒性和抗病毒活性评估

Evaluation of cytotoxicity and antiviral activity of Decne leaves extract against influenza A/PR/8/34 (H1N1).

作者信息

Albeshri Abdulaziz, Baeshen Nabih A, Bouback Thamer A, Aljaddawi Abdullah A

机构信息

King Abdulaziz University, Faculty of science, biological sciences department, Jeddah 21589, Saudi Arabia.

Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in Biotechnology, King Abdul-Aziz University, Jeddah 21589, Saudi Arabia.

出版信息

Saudi J Biol Sci. 2022 Sep;29(9):103375. doi: 10.1016/j.sjbs.2022.103375. Epub 2022 Jul 16.

Abstract

Influenza viruses have developed resistance to the current classes of drugs, which means they could eventually become more virulent and cause more mortality and hospitalization. Our study aims to investigate the antiviral activity of Decne leaves extract in vitro and search for new promising drugs from identified compounds in silico. The study was performed in vitro by utilizing Madin-Darby Canine Kidney cell line (MDCK) as a substrate for the influenza virus and estimating the inhibition performance of the plant leaves extract. Additionally, in silico screening was conducted to explore the antiviral activity of phytochemicals. We investigated the cytotoxicity of leaves extract and its antiviral activity against influenza virus (A/Puerto Rico/8/34 (H1N1)) using the MTT assay. The mode of action of the plant leaves extract during the viral life cycle was tested using time-of-addition assay. In silico analyses were performed, including molecular docking, drug-likeness analysis, and toxicity risk assessment, to state the leading compounds to be developed into an anti-influenza virus drug. The 50% cytotoxicity concentration of the leaves extract was CC50: 184.6 µg/mL, and the 50% inhibition concentration was CI50: 19.71 µg\mL. The time of addition assay revealed that leaves extract exerted its activity in the late step of the influenza virus replication cycle. In comparison to Oseltamivir, the leading compounds showed better binding affinity and can be developed into oral drugs with low toxicity risk. Isolation and purification of the leading compounds and testing their antiviral activity in vitro and in vivo are required.

摘要

流感病毒已对目前的各类药物产生耐药性,这意味着它们最终可能会变得更具毒性,导致更多的死亡和住院病例。我们的研究旨在调查地锦叶提取物的体外抗病毒活性,并从计算机模拟鉴定出的化合物中寻找新的有前景的药物。该研究通过利用犬肾传代细胞系(MDCK)作为流感病毒的底物并评估植物叶提取物的抑制性能在体外进行。此外,还进行了计算机模拟筛选以探索植物化学物质的抗病毒活性。我们使用MTT法研究了叶提取物的细胞毒性及其对流感病毒(A/波多黎各/8/34(H1N1))的抗病毒活性。使用加样时间试验测试了植物叶提取物在病毒生命周期中的作用模式。进行了计算机模拟分析,包括分子对接、类药性分析和毒性风险评估,以确定可开发成抗流感病毒药物的先导化合物。叶提取物的50%细胞毒性浓度为CC50:184.6µg/mL,50%抑制浓度为CI50:19.71µg/mL。加样时间试验表明,叶提取物在流感病毒复制周期的后期发挥其活性。与奥司他韦相比,先导化合物表现出更好的结合亲和力,并且可以开发成低毒性风险的口服药物。需要对先导化合物进行分离和纯化,并在体外和体内测试它们的抗病毒活性。

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