Antiviral effect in association with anti-apoptosis and anti-autophagy of repurposing formoterol fumarate dihydrate on enterovirus A71-infected neuronal cells

被引:1
作者
Jintana, Kachaporn [1 ]
Prasertsopon, Jarunee [1 ]
Puthavathana, Pilaipan [1 ]
Lerdsamran, Hatairat [1 ]
机构
[1] Mahidol Univ, Fac Med Technol, Ctr Res & Innovat, Nakhon Pathom 73170, Thailand
关键词
Enterovirus A71; Formoterol fumarate dihydrate; Antiviral; Anti-apoptosis; Anti-autophagy; NEUROLOGICAL DISEASE; INHIBITORS; INFECTION; REPLICATION; BUDESONIDE; MICE;
D O I
10.1016/j.virusres.2022.198692
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Objective: To investigate antiviral activity, anti-apoptosis and anti-autophagy associated with antiviral effect of repurposing formoterol fumarate dihydrate (FFD) against enterovirus A71 (EV-A71) infection in human neuroblastoma cells. Methods: In vitro antiviral effects of FFD against EV-A71 infection were examined in human neuroblastoma SK-NSH cells. The impacts on EV-A71 replication were evaluated by progeny virus production, viral RNA synthesis, and viral protein expression. The target of action of FFD against EV-A71 was determined from the effective stage by time-of-addition assay. Moreover, the anti-apoptosis and anti-autophagy activities associated with antiviral effect were observed by detection of apoptosis-and autophagy-related proteins. Results: FFD significantly inhibited EV-A71 replication in neuronal cells through interfering the early stages of replication cycle which might be the steps during uncoating to viral protein synthesis. Additionally, FFD culminated in reducing of EV-A71-induced apoptosis and autophagy with caspase-3-cleaved form and LC3-II expression levels showed markedly decreased while increasing of Bcl-2 and mTOR expression levels. These might indicate the neuroprotective effect of FFD on EV-A71-induced apoptosis and autophagy. Conclusions: Preliminary mode of action studies showed that repurposing FFD significantly inhibited EV-A71 replication at early stage of viral replication and exhibited anti-apoptosis and anti-autophagy activities in neuronal cells. These findings may provide an opportunity, via drug repurposing of FFD, for a candidate antiviral drug against EV-A71 infection.
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页数:13
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共 43 条
  • [1] Characteristics of enterovirus 71-induced cell death and genome scanning to identify viral genes involved in virus-induced cell apoptosis
    Bai, Jinjin
    Chen, Xixi
    Liu, Qingqing
    Zhou, Xin
    Long, Jian-Er
    [J]. VIRUS RESEARCH, 2019, 265 : 104 - 114
  • [2] Phylogenetic designation of enterovirus 71 genotypes and subgenotypes using complete genome sequences
    Chan, Yoke-Fun
    Sam, I-Ching
    AbuBakar, Sazaly
    [J]. INFECTION GENETICS AND EVOLUTION, 2010, 10 (03) : 404 - 412
  • [3] Retrograde axonal transport: a major transmission route of enterovirus 71 in mice
    Chen, Che-Szu
    Yao, Yi-Chuan
    Lin, Shin-Chao
    Lee, Yi-Ping
    Wang, Ya-Fang
    Wang, Jen-Ren
    Liu, Ching-Chuan
    Lei, Huan-Yao
    Yu, Chun-Keung
    [J]. JOURNAL OF VIROLOGY, 2007, 81 (17) : 8996 - 9003
  • [4] Enterovirus 71 triggering of neuronal apoptosis through activation of Abl-Cdk5 signalling
    Chen, Tsan-Chi
    Lai, Yiu-Kay
    Yu, Chun-Keung
    Juang, Jyh-Lyh
    [J]. CELLULAR MICROBIOLOGY, 2007, 9 (11) : 2676 - 2688
  • [5] The correlation between the presence of viremia and clinical severity in patients with enterovirus 71 infection: a multi-center cohort study
    Cheng, Hao-Yuan
    Huang, Yi-Chuan
    Yen, Ting-Yu
    Hsia, Shao-Hsuan
    Hsieh, Yu-Chia
    Li, Chung-Chen
    Chang, Luan-Yin
    Huang, Li-Min
    [J]. BMC INFECTIOUS DISEASES, 2014, 14
  • [6] Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax
    Cong, Haolong
    Du, Ning
    Yang, Yang
    Song, Lei
    Zhang, Wenliang
    Tien, Po
    [J]. JOURNAL OF VIROLOGY, 2016, 90 (21) : 9862 - 9877
  • [7] Antiviral activity of caspase inhibitors: effect on picornaviral 2A proteinase
    Deszcz, L
    Selpelt, J
    Vassilieva, E
    Roetzer, A
    Kuechler, E
    [J]. FEBS LETTERS, 2004, 560 (1-3): : 51 - 55
  • [8] FORMOTEROL - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC POTENTIAL IN REVERSIBLE OBSTRUCTIVE AIRWAYS DISEASE
    FAULDS, D
    HOLLINGSHEAD, LM
    GOA, KL
    [J]. DRUGS, 1991, 42 (01) : 115 - 137
  • [9] Discovery of Itraconazole with Broad-Spectrum In Vitro Antienterovirus Activity That Targets Nonstructural Protein 3A
    Gao, Qianqian
    Yuan, Shilin
    Zhang, Chao
    Wang, Ying
    Wang, Yizhuo
    He, Guimei
    Zhang, Shuyi
    Altmeyer, Ralf
    Zou, Gang
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (05) : 2654 - 2665
  • [10] Regulation Mechanisms and Signaling Pathways of Autophagy
    He, Congcong
    Klionsky, Daniel J.
    [J]. ANNUAL REVIEW OF GENETICS, 2009, 43 : 67 - 93