2. Academic Validation
  3. Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1

Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1

  • Virulence. 2018 Jan 1;9(1):588-603. doi: 10.1080/21505594.2017.1421893.
Wei-Chun Chen 1,  Chin-Kai Tseng 2 3,  Chun-Kuang Lin 4,  Shen-Nien Wang 5 6,  Wen-Hung Wang 7,  Shih-Hsien Hsu 1,  Yu-Hsuan Wu 2 3,  Ling-Chien Hung 8 9,  Yen-Hsu Chen 8 9 10 11,  Jin-Ching Lee 1 12 13 14 15
Affiliations

Affiliations

  • 1 a Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung , Taiwan.
  • 2 b Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University , Tainan , Taiwan.
  • 3 c Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University , Tainan , Taiwan.
  • 4 d Doctoral Degree Program in Marine Biotechnology, College of Marine Sciences, National Sun Yat-Sen University , Kaohsiung , Taiwan.
  • 5 e Division of Hepatobiliary Surgery , Department of Surgery, Kaohsiung Medical University Hospital , Kaohsiung Taiwan.
  • 6 f Department of Surgery , Faculty of Medicine, Kaohsiung Medical University Hospital , Kaohsiung Taiwan.
  • 7 g Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan.
  • 8 h Division of Infectious Diseases , Department of Internal Medicine, Kaohsiung Medical University Hospital , Kaohsiung , Taiwan.
  • 9 i School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, Center for Dengue Fever Control and Research, Kaohsiung Medical University , Kaohsiung , Taiwan.
  • 10 j Department of Biological Science and Technology , College of Biological Science and Technology, National Chiao Tung University , HsinChu , Taiwan.
  • 11 k Center for Infectious Disease and Cancer Research, Kaohsiung Medical University , Kaohsiung , Taiwan.
  • 12 l Department of Biotechnology , College of Life Science, Kaohsiung Medical University , Kaohsiung , Taiwan.
  • 13 m Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung , Taiwan.
  • 14 n Research Center for Natural Products and Drug Development, Kaohsiung Medical University , Kaohsiung , Taiwan.
  • 15 o Department of Medical Research , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan.
PMID: 29338543 DOI: 10.1080/21505594.2017.1421893
Abstract

Dengue virus (DENV) Infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV Infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice. Then, the anti-DENV activity of lucidone was confirmed by western blotting and quantitative-reverse-transcription-polymerase chain reaction analysis, with an EC50 value of 25 ± 3 μM. Lucidone significantly induced heme oxygenase-1 (HO-1) production against DENV replication by inhibiting DENV NS2B/3 protease activity to induce the DENV-suppressed Antiviral interferon response. The inhibitory effect of lucidone on DENV replication was attenuated by silencing of HO-1 gene expression or blocking HO-1 activity. In addition, lucidone-stimulated nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in transactivation of HO-1 expression for its anti-DENV activity. Taken together, the mechanistic investigations revealed that lucidone exhibits significant anti-DENV activity in in vivo and in vitro by inducing Nrf2-mediated HO-1 expression, leading to blockage of viral protease activity to induce the anti-viral interferon (IFN) response. These results suggest that lucidone is a promising candidate for drug development.

Keywords

Dengue virus; heme oxygnase-1; interferon response; lucidone; viral replication.

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