Antiviral activity of micafungin against enterovirus 71.
BACKGROUND
Enterovirus 71 (EV71) is a major causative agent of hand-foot-mouth disease (HFMD) and also causes severe neurological complications, leading to fatality in young children. However, no effective therapy is currently available for the treatment of this infection.


METHODS
We identified small-molecule inhibitors of EV71 from a screen of 968 Food and Drug Administration (FDA)-approved drugs, with which clinical application for EV71-associated diseases would be more feasible, using EV71 subgenomic replicon system. Primary hits were extensively evaluated for their antiviral activities in EV71-infected cells.


RESULTS
We identified micafungin, an echinocandin antifungal drug, as a novel inhibitor of EV71. Micafungin potently inhibits the proliferation of EV71 as well as the replication of EV71 replicon in cells with a low micromolar IC50 (~5 μM). The strong antiviral effect of micafungin on EV71 replicon and the result from time-of-addition experiment demonstrated a targeting of micafungin on virion-independent intracellular process(es) during EV71 infection. Moreover, an extensive analysis excluded the involvement of 2C and 3A proteins, IRES-dependent translation, and also that of polyprotein processing in the antiviral effect of micafungin.


CONCLUSIONS
Our research revealed a new indication of micafungin as an effective inhibitor of EV71, which is the first case reporting antiviral activity of micafungin, an antifungal drug.
Virus Research and Testing Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, South Korea.
Chonsaeng
C
Kim
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, South Korea.|College of Pharmacy, Chungbuk National University, 1 Chungdae-ro Seowon-gu, Cheongju-si, Chungcheongbuk-do, 28644, South Korea.
Hyunju
H
Kang
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, South Korea.|College of Pharmacy, Chungbuk National University, 1 Chungdae-ro Seowon-gu, Cheongju-si, Chungcheongbuk-do, 28644, South Korea.
Dong-Eun
DE
Kim
Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, 1 Gangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, South Korea.
Jae-Hyoung
JH
Song
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, South Korea.
Miri
M
Choi
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, South Korea.
Mingu
M
Kang
Virus Research and Testing Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, South Korea.
Kyungjin
K
Lee
Virus Research and Testing Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, South Korea.
Hae Soo
HS
Kim
Virus Research and Testing Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, South Korea.
Jin Soo
JS
Shin
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, South Korea.
Hyejeong
H
Jeong
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, South Korea.
Sunhee
S
Jung
College of Pharmacy, Chungbuk National University, 1 Chungdae-ro Seowon-gu, Cheongju-si, Chungcheongbuk-do, 28644, South Korea.
Sang-Bae
SB
Han
Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, South Korea.
Jong Heon
JH
Kim
Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, 1 Gangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, South Korea.
Hyun-Jeong
HJ
Ko
Virus Research and Testing Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, South Korea.
Chong-Kyo
CK
Lee
Virus Research and Testing Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, South Korea.
Meehyein
M
Kim
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, South Korea. sungchan@kribb.re.kr.|Department of Biomolecular Science, Korea University of Science and Technology, 217 Gajeong-ro, Daejeon, 34113, South Korea. sungchan@kribb.re.kr.
Sungchan
S
Cho
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D058492:Drug Repositioning; D054714:Echinocandins / Q000494:pharmacology*; D029821:Enterovirus A, Human / Q000187:drug effects*; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin
D000998:Antiviral Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin
Antiviral drug; Enterovirus; Enterovirus 71 (EV71); FDA-approved drug; Micafungin