Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Quercetin-3-Methyl Ether Induces Early Apoptosis to Overcome HRV1B Immune Evasion, Suppress Viral Replication, and Mitigate Inflammatory Pathogenesis

  • Jae-Hyoung Song (Department of Pharmacy, Kangwon National University) ;
  • Seo-Hyeon Mun (Department of Pharmacy, Kangwon National University) ;
  • Sunil Mishra (College of Pharmacy, Yeungnam University) ;
  • Seong-Ryeol Kim (Division of Acute Viral Diseases, Centers for Emerging Virus Research, National Institute of Health, Korea Disease Control and Prevention Agency) ;
  • Heejung Yang (Department of Pharmacy, Kangwon National University) ;
  • Sun Shim Choi (Division of Biomedical Convergence, College of Biomedical Science, Institue od Bioscience & Biotechnology, Kangwon National University) ;
  • Min-Jung Kim (Department of Pharmacy, Kangwon National University) ;
  • Dong-Yeop Kim (Division of Biomedical Convergence, College of Biomedical Science, Institue od Bioscience & Biotechnology, Kangwon National University) ;
  • Sungchan Cho (Nucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Youngwook Ham (Nucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hwa-Jung Choi (Department of Beauty Art, Youngsan University) ;
  • Won-Jin Baek (Department of Beauty Art, Youngsan University) ;
  • Yong Soo Kwon (Department of Pharmacy, Kangwon National University) ;
  • Jae-Hoon Chang (College of Pharmacy, Yeungnam University) ;
  • Hyun-Jeong Ko (Department of Pharmacy, Kangwon National University)
  • Received : 2024.10.30
  • Accepted : 2025.01.02
  • Published : 2025.03.01
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Abstract

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education (RS-2022-NR074811). This research was further supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (RS-2023-KH134750, HI23C0195). We would like to thank Editage (www.editage.co.kr) for English language editing.

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