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Article

Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2

1
Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600, Taiwan
2
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
3
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
4
Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung Medical Center, Keelung 204, Taiwan
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Program in Molecular Medicine, School of Life Sciences, National Yang-Ming University, Taipei 112, Taiwan
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Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
7
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
8
Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 300, Taiwan
9
Division of Big Data, Phalanx Biotech Group, Hsinchu 300, Taiwan
10
Department of Animal Science and Biotechnology, Tunghai University, Taichung 407, Taiwan
11
Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
12
Center for Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
13
M. Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Cheng-Wen Lin
Viruses 2021, 13(2), 308; https://doi.org/10.3390/v13020308
Received: 2 January 2021 / Revised: 9 February 2021 / Accepted: 13 February 2021 / Published: 16 February 2021
(This article belongs to the Special Issue Broad-Spectrum Antiviral Agents)
Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication. View Full-Text
Keywords: honeysuckle; let-7a; EV71; virus replication honeysuckle; let-7a; EV71; virus replication
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MDPI and ACS Style

Lee, Y.-R.; Chang, C.-M.; Yeh, Y.-C.; Huang, C.-Y.F.; Lin, F.-M.; Huang, J.-T.; Hsieh, C.-C.; Wang, J.-R.; Liu, H.-S. Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2. Viruses 2021, 13, 308. https://doi.org/10.3390/v13020308

AMA Style

Lee Y-R, Chang C-M, Yeh Y-C, Huang C-YF, Lin F-M, Huang J-T, Hsieh C-C, Wang J-R, Liu H-S. Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2. Viruses. 2021; 13(2):308. https://doi.org/10.3390/v13020308

Chicago/Turabian Style

Lee, Ying-Ray, Chia-Ming Chang, Yuan-Chieh Yeh, Chi-Ying F. Huang, Feng-Mao Lin, Juan-Ting Huang, Chang-Chi Hsieh, Jen-Ren Wang, and Hsiao-Sheng Liu. 2021. "Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2" Viruses 13, no. 2: 308. https://doi.org/10.3390/v13020308

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