Schisandrin A inhibits dengue viral replication via upregulating antiviral interferon responses through STAT signaling pathway.
Dengue virus (DENV) infects 400 million people worldwide annually. Infection of more than one serotype of DENV highly corresponds to dengue hemorrhagic fever and dengue shock syndrome, which are the leading causes of high mortality. Due to lack of effective vaccines and unavailable therapies against DENV, discovery of anti-DENV agents is urgently needed. We first characterize that Schisandrin A can inhibit the replication of four serotypes of DENV in a concentration- and time-dependent manner, with an effective half-maximal effective concentration 50% (EC50) value of 28.1 ± 0.42 μM against DENV serotype type 2 without significant cytotoxicity. Furthermore, schisandrin A can effectively protect mice from DENV infection by reducing disease symptoms and mortality of DENV-infected mice. We demonstrate that STAT1/2-mediated antiviral interferon responses contribute to the action of schisandrin A against DENV replication. Schisandrin A represents a potential antiviral agent to block DENV replication in vitro and in vivo. In conclusion, stimulation of STAT1/2-mediated antiviral interferon responses is a promising strategy to develop antiviral drug.
Department of Chinese Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan.|Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan.
Jung-Sheng
JS
Yu
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yu-Hsuan
YH
Wu
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chin-Kai
CK
Tseng
Doctoral Degree Program in Marine Biotechnology, College of Marine Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Chun-Kuang
CK
Lin
Department of Chinese Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan.
Yao-Chin
YC
Hsu
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University, Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Dengue Fever Control and Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yen-Hsu
YH
Chen
Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.|Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jin-Ching
JC
Lee
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D034242:Cyclooctanes / Q000494:pharmacology* / Q000627:therapeutic use; D003715:Dengue / Q000188:drug therapy*; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D011083:Polycyclic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; D050791:STAT Transcription Factors; C034734:schizandrin A; D007372:Interferons