Discovery of 10-Shogaol from Zingiber officinale with Broad Antiviral and Anti-inflammatory Activity against Dengue and Zika Viruses Using Activity-Guided Molecular Networking

  • J Agric Food Chem. 2026 Jun 24;74(24):18723-18740. doi: 10.1021/acs.jafc.6c01060.
Mengxue Li  1 ,  Renyu Zhou  1 ,  Lei Guo  1 ,  Yifeng Liu  1 ,  Daiqiang Lu  1 ,  Hao Chen  1 ,  Wei Xu  2 ,  Jiaojiao Peng  1  3 ,  Wenjiao Wu  4 ,  Jianhai Yu  5 ,  Liangliang He  6 ,  Feng Gao  1  3 ,  Qiao Zhang  1  3
Affiliations
  • 1. Institute of Molecular and Medical Virology, School of Medicine, Jinan University, Guangzhou510632, China.
  • 2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou510515, China.
  • 3. Key Laboratory of Viral Pathogenesitables & Infection Prevention and Control(Jinan University), Ministry of Education, Guangzhou510632, China.
  • 4. Department of Pharmacy, Jinan University Affiliated Guangdong Second General Provincial Hospital, Guangzhou510317, China.
  • 5. Department of Biosafety Level 3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, Key Laboratory of Infectious Diseases Research in South China, School of Public Health, Southern Medical University, Guangzhou510515, China.
  • 6. State Key Laboratory of Bioactive Molecules and Druggability Assessment, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou510632, China.
PMID: 42270434 DOI: 10.1021/acs.jafc.6c01060
Abstract

The bioactive constituents of ginger (Zingiber officinale Roscoe) display well-documented immunomodulatory and antimicrobial effects; however, the role of these components in combating Dengue Virus (DENV) and Other flaviviruses Infection remains unknown. Here, activity-guided molecular networking and Antiviral screening identified 10-shogaol as the primary Antiviral phytochemical in ginger, with a half-maximal inhibitory concentration (IC50) value of 2.502 μM. Mechanistically, 10-shogaol bound the n-octyl-β-d-glucopyranoside (β-OG) pocket of viral envelope protein (E), interfering with viral attachment and conferring broad Antiviral properties against DENV and Zika virus (ZIKV). Additionally, 10-shogaol suppressed proinflammatory cytokines and mitigated tissue damage in mice by acting as a novel Nrf2 activator by inhibiting Keap1-mediated ubiquitination and Proteasome degradation. Activation of Nrf2 by 10-shogaol induced antioxidant gene expression and inhibited inflammatory NF-κB signaling. Collectively, our study suggests that 10-shogaol acts as a broad-spectrum entry inhibitor against DENV and ZIKV as well as confers anti-inflammatory benefits for mitigating virus-induced inflammatory tissue damage.

Keywords
10-shogaol; DENV; Nrf2 activation; ZIKV; activity-guided molecular networking; entry inhibitor.
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