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The in vitro and in vivo antiviral effects of aloperine against Zika virus infection

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机构: [1]Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China. [2]Foshan Institute of Medical Microbiology, Foshan, China. [3]Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China. [4]Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Shenzhen, China. [5]The First Affiliated Hospital of Jinan University, Guangzhou, China. [6]Jiangsu Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, Suzhou, China. [7]Medical Research Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
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关键词: aloperine antiviral action RdRp inhibitor Zika virus

摘要:
Zika virus (ZIKV) infection poses a significant threat to global public health and is associated with microcephaly. There are no approved ZIKV-specific vaccines or drugs for the clinical treatment of the infection. Currently, there are no approved ZIKV-specific vaccines or drugs for the clinical treatment of the infection. In this study, we investigated the antiviral potential of aloperine, a quinolizidine alkaloid, against ZIKV infection in vivo and in vitro. Our results demonstrate that aloperine effectively inhibits ZIKV infection in vitro, with a low nanomolar half maximal effective concentration (EC50 ). Specifically, aloperine strongly protected cells from ZIKV multiplication, as indicated by decreased expression of viral proteins and virus titer. Our further investigations using the time-of-drug-addition assay, binding, entry, and replication assays, detection of ZIKV strand-specific RNA, the cellular thermal shift assay, and molecular docking revealed that aloperine significantly inhibits the replication stage of the ZIKV life cycle by targeting the domain RNA-dependent RNA polymerase (RDRP) of ZIKV NS5 protein. Additionally, aloperine reduced viremia in mice and effectively lowered the mortality rate in infected mice. These findings highlight the potency of aloperine and its ability to target ZIKV infection, suggesting its potential as a promising antiviral drug against ZIKV.© 2023 Wiley Periodicals LLC.

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出版当年[2022]版:
大类 | 3 区 医学
小类 | 3 区 病毒学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 病毒学
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出版当年[2021]版:
Q1 VIROLOGY
最新[2023]版:
Q1 VIROLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China. [2]Foshan Institute of Medical Microbiology, Foshan, China. [3]Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
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通讯机构: [1]Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China. [2]Foshan Institute of Medical Microbiology, Foshan, China. [3]Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China. [4]Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Shenzhen, China.
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