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Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection

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资源类型：
Pubmed体系：
作者：
Li Jinhua[1] * ; Zhao Yao[3] ; Dai Ying[4] ; Zhao Junning[1,2,*1] ;
机构： [1]Department of Pharmacognosy, West China School of Pharmacy, Sichuan University, Chengdu 610041, China [2]National Key Laboratory of Drug Regulatory Science, National Medical Products Administration (NMPA), Beijing 100038, China [3]Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China [4]Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, Sichuan 610041, China
出处：
DOI： 10.1016/j.virusres.2023.199223
ISSN：

关键词： γ-Fagarine hMPV Antiviral activity Lysosome HSPG

摘要：
Human metapneumovirus (hMPV) causes significant upper and lower respiratory disease in all age groups worldwide. However, there is no licensed drugs or vaccine available against hMPV. γ-Fagarine, an alkaloid isolated from the root of zanthoxylum, has been reported to be effective in the treatment of cancer, inflammatory diseases and antivirals. However, little is known about the inhibitory effect of γ-Fagarine against respiratory virus infection and the mechanism. In this study, we aim to investigate the effect of γ-Fagarine on hMPV infection and explore its underlying molecular mechanisms. Vero-E6 and 16HBE cells were used as cell models. Virus replication and microcosm character were explored in Vero-E6 cells. Then, the antiviral activities were investigated by quantitative real-time PCR (RT-qPCR), western blotting (WB), and indirect immunofluorescence assays (IFAs) in Vero-E6 and 16HBE. Potential mechanisms of γ-Fagarine related to HSPG and lysosome pH were assessed in 16HBE cells. Lastly, a virus-infected mouse model was established and antiviral assay in vivo was conducted. γ-Fagarine showed no toxicity toward Vero-E6 cells and 16HBE cells but demonstrated anti-hMPV activity. Virus titers of γ-Fagarine group were reduced to 33% and 45% of the hMPV groups, respectively. Besides, mechanistic studies revealed that γ-Fagarine could inhibit hMPV by dual mechanisms of direct restraining virus binding with HSPG and influencing lysosome pH. Furthermore, oral delivery of γ-Fagarine to hMPV-infected mice at a dosage of 25 mg/kg reduced the hMPV load in lung tissues. After γ-Fagarine treatment, pathological damage caused by viral infection was also ameliorated. These findings suggest that γ-Fagarine has antiviral effects in vitro and in vivo, which are associated with its ability to restrain virus binding with HSPG and influence lysosome pH, thus indicating that γ-Fagarine has the potential to serve as a candidate to fight against hMPV infection and other respiratory viruses such as influenza viruses and SARS-CoV-2.Copyright © 2023. Published by Elsevier B.V.

基金：
The Project of Sichuan Provincial Administration of Traditional Chinese Medicine (2020YSHB01) and Major Scientific and Technological Projects of Sichuan Provincial Administration of Traditional Chinese Medicine (2021XYCZ001).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 4 区 医学
小类 | 4 区 病毒学
最新[2023]版：
大类 | 4 区 医学
小类 | 4 区 病毒学
第一作者：
第一作者机构： [1]Department of Pharmacognosy, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
通讯作者：
通讯机构： [1]Department of Pharmacognosy, West China School of Pharmacy, Sichuan University, Chengdu 610041, China [2]National Key Laboratory of Drug Regulatory Science, National Medical Products Administration (NMPA), Beijing 100038, China [*1]Department of Pharmacognosy, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
推荐引用方式(GB/T 7714)：
Li Jinhua,Zhao Yao,Dai Ying,et al.Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection[J].Virus research.2023,336:199223.doi:10.1016/j.virusres.2023.199223.
APA：
Li Jinhua,Zhao Yao,Dai Ying&Zhao Junning.(2023).Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection.Virus research,336,
MLA：
Li Jinhua,et al."Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection".Virus research 336.(2023):199223

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