2. Academic Validation
  3. Sofalcone Suppresses Dengue Virus Replication by Activating Heme Oxygenase-1-Mediated Antiviral Interferon Responses

Sofalcone Suppresses Dengue Virus Replication by Activating Heme Oxygenase-1-Mediated Antiviral Interferon Responses

  • Int J Mol Sci. 2025 Jun 20;26(13):5921. doi: 10.3390/ijms26135921.
Yu-Lun Ou 1 2,  Wei-Chun Chen 3,  Chia-Hung Yen 4,  Wangta Liu 3,  Chun-Kuang Lin 5,  Shun-Chieh Yu 6,  Mei-Yueh Lee 2 7 8,  Jin-Ching Lee 3 4 5 6 9
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
  • 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
  • 3 Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 4 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 5 Department of Marine Biotechnology and Resources, College of Marine Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
  • 6 Department of Biological Sciences, Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
  • 7 Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Gangshan Hospital, Kaohsiung 807378, Taiwan.
  • 8 Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 9 Center for Tropical Medicine and Infectious Disease Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
PMID: 40649701 DOI: 10.3390/ijms26135921
Abstract

Dengue Virus (DENV) Infection is strongly associated with dengue hemorrhagic fever and dengue shock syndrome, both of which carry mortality risks. Addressing the urgent need for effective dengue therapeutics, we identified sofalcone, a gastroprotective agent with antioxidant and anti-inflammatory properties, as a potential inhibitor of DENV replication. Sofalcone demonstrated efficacy against all four DENV serotypes, with the dose inhibiting 50% (IC50) value of 28.1 ± 0.42 μM against viral replication of DENV serotype 2, without significant cytotoxicity. Additionally, sofalcone significantly improved survival rates and reduced viral titers in DENV-infected ICR-suckling mice. Mechanistically, sofalcone induced heme oxygenase-1 (HO-1) expression via the nuclear factor-erythroid 2-reated factor 2 (Nrf2) pathway, which in turn suppressed viral protease activity and restored Antiviral interferon (IFN) responses. This included dose-dependent stimulation of IFN downstream Antiviral genes such as 2'-5'-oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3. Given its established clinical use as an anti-gastric ulcer drug, sofalcone offers promising potential for rapid application in treating DENV Infection.

Keywords

dengue virus; heme oxygenase-1; interferon; sofalcone.

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