2. Academic Validation
  3. An estrogen antagonist, cyclofenil, has anti-dengue-virus activity

An estrogen antagonist, cyclofenil, has anti-dengue-virus activity

  • Arch Virol. 2019 Jan;164(1):225-234. doi: 10.1007/s00705-018-4079-0.
Daiki Tohma 1 2,  Shigeru Tajima 3,  Fumihiro Kato 1,  Hirotaka Sato 4 5,  Michinori Kakisaka 5,  Takayuki Hishiki 6,  Michiyo Kataoka 7,  Haruko Takeyama 2,  Chang-Kweng Lim 1,  Yoko Aida 4 5,  Masayuki Saijo 1
Affiliations

Affiliations

  • 1 Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan.
  • 2 Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsucho, Shinjuku, Tokyo, 162-8480, Japan.
  • 3 Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan. stajima@nih.go.jp.
  • 4 Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
  • 5 Virus Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
  • 6 Department of Microbiology, Kanagawa Prefectural Institute of Public Health, 1-3-1 Shimomachiya, Chigasaki, Kanagawa, 253-0087, Japan.
  • 7 Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan.
PMID: 30357482 DOI: 10.1007/s00705-018-4079-0
Abstract

Dengue virus (DENV) infections are a major cause of morbidity and mortality in tropical and subtropical areas. Several compounds that act against DENV have been studied in clinical trials to date; however, there have been no compounds identified that are effective in reducing the severity of the clinical manifestations. To explore anti-DENV drugs, we examined small molecules that interact with DENV NS1 and inhibit DENV replication. Cyclofenil, which is a selective Estrogen receptor Modulator (SERM) and has been used clinically as an ovulation-inducing drug, showed an inhibitory effect on DENV replication in mammalian cells but not in mosquito cells. Other SERMs also inhibited DENV replication in mammalian cells, but cyclofenil showed the weakest cytotoxicity among these SERMs. Cyclofenil also inhibited the replication of Zika virus. A time-of-addition assay suggested that cyclofenil may interfere with two stages of the DENV life cycle: the translation-RNA synthesis and assembly-maturation stages. However, the level of intracellular infectious particles decreased more drastically after treatment with cyclofenil than the viral RNA level did, indicating that the assembly-maturation stage might be the main target of cyclofenil. In electron microscopy analysis, many aggregated particles were detected in DENV-infected cells in the presence of cyclofenil, supporting the possibility that cyclofenil impedes the process of assembly and maturation of DENV.

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