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Article

Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability

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School of Pharmacy, National Defense Medical Center (NDMC), No. 161, Section 6, Minquan East Road, Taipei 114, Taiwan
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Department of Biological Sciences, National University of Singapore (NUS), 14 Science Drive 4, Singapore 117543, Singapore
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School of Life Science, National Taiwan Normal University (NTNU), No. 88, Ting-Chow Road, Section 4, Taipei 116, Taiwan
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Institute of Preventive Medicine, National Defense Medical Center (NDMC), No. 172, Dapu Road, New Taipei City 237, Taiwan
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Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital (TSGH), National Defense Medical Center (NDMC), No. 161, Section 6, Minquan East Road, Taipei 114, Taiwan
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Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital (TSGH), National Defense Medical Center (NDMC), No. 161, Section 6, Minquan East Road, Taipei 114, Taiwan
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Graduate Institute of Life Sciences, National Defense Medical Center (NDMC), No. 161, Section 6, Minquan East Road, Taipei 114, Taiwan
*
Author to whom correspondence should be addressed.
Y.-C.C. and J.-W.L. contributed equally to this work.
Academic Editor: Juan Carlos Saiz
Pharmaceuticals 2021, 14(4), 338; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040338
Received: 21 March 2021 / Revised: 3 April 2021 / Accepted: 6 April 2021 / Published: 7 April 2021
(This article belongs to the Special Issue Current Trends in RNA Virus Vaccines)
Dengue fever is an arbovirus disease caused by infection with the dengue virus (DENV). Half of the world’s population lives under the threat of dengue fever, however, researchers have yet to develop any drugs that are clinically applicable to this infection. Micafungin is a member of the echinocandins family of anti-fungal drugs, capable of blocking the synthesis of β-1,3-D-glucan in the walls of fungal cells. Previous studies have demonstrated the effectiveness of Micafungin against infections of enterovirus 71 (EV71) and chikungunya virus (CHIKV). This is the first study demonstrating the effectiveness of micafungin in inhibiting the cytopathic effects of dengue virus serotype 2 (DENV-2) in a dose-dependent manner. Time-of-addition assays verified the inhibitory effects of micafungin in pre-treated, co-treated, and full-treatment groups. Binding and entry assays also demonstrated the effectiveness of micafungin in the early stage of DENV-2 infection. The virucidal efficacy of micafungin appears to lie in its ability to destroy the virion. Molecular docking assays revealed the binding of micafungin to the envelope protein of DENV-2, thereby revealing the mechanism by which micafungin affects the early stage of DENV infection and the stability of DENV. Two other micafungin analogs, caspofungin and anidulafungin, were also shown to have the antiviral effects on DENV-2. Finally, immunofluorescence assay (IFA) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the broad anti-DENV ability of micafungin against dengue virus serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). Taken together, these results demonstrate the potential of micafungin and its analogs as candidates for the development of broad-spectrum treatments for DENV infection. View Full-Text
Keywords: antiviral; dengue virus; micafungin; echinocandins; binding; entry and virucidal antiviral; dengue virus; micafungin; echinocandins; binding; entry and virucidal
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MDPI and ACS Style

Chen, Y.-C.; Lu, J.-W.; Yeh, C.-T.; Lin, T.-Y.; Liu, F.-C.; Ho, Y.-J. Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability. Pharmaceuticals 2021, 14, 338. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040338

AMA Style

Chen Y-C, Lu J-W, Yeh C-T, Lin T-Y, Liu F-C, Ho Y-J. Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability. Pharmaceuticals. 2021; 14(4):338. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040338

Chicago/Turabian Style

Chen, Yen-Chen, Jeng-Wei Lu, Chia-Tsui Yeh, Te-Yu Lin, Feng-Cheng Liu, and Yi-Jung Ho. 2021. "Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability" Pharmaceuticals 14, no. 4: 338. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040338

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