2. Academic Validation
  3. Bisbenzylisoquinoline alkaloids inhibit influenza virus replication by disrupting endosomal acidification

Bisbenzylisoquinoline alkaloids inhibit influenza virus replication by disrupting endosomal acidification

  • Virol J. 2025 Jun 4;22(1):181. doi: 10.1186/s12985-025-02775-x.
Bo Li 1,  Lijun Qiao 1 2,  Xingqiong Li 1 2,  Ge Yang 1,  Kun Wang 1,  Huiqiang Wang 1,  Shuo Wu 1 2,  Haiyan Yan 3,  Jiandong Jiang 1 2,  Yuhuan Li 4 5
Affiliations

Affiliations

  • 1 CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Technology and Application for Anti-Infective New Drugs Research and Development, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 2 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 3 CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Technology and Application for Anti-Infective New Drugs Research and Development, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. yan0495@163.com.
  • 4 CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Technology and Application for Anti-Infective New Drugs Research and Development, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. yuhuanlibj@126.com.
  • 5 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. yuhuanlibj@126.com.
PMID: 40468427 DOI: 10.1186/s12985-025-02775-x
Abstract

Influenza Virus, known for causing recurrent epidemics and pandemics, pose a significant public health challenge due to their rapid mutation rates and the emergence of drug resistance. This emphasizes the urgent need for the development of novel Antiviral drugs. In this study, we identified five Bisbenzylisoquinoline Alkaloids (BBAs)-cepharanthine (CEP), tetrandrine (TET), fangchinoline (FCN), berbamine (BBM) and iso-tetrandrine (Iso-TET)-that exhibit Antiviral activity against Influenza Virus, as determined through cytopathic effect inhibition screening. These compounds showed dose-dependent suppression of viral replication by targeting the early stages of the viral life cycle, specifically through disruption of endosomal acidification and inhibition of viral genome release into the cytoplasm. Notably, treatment with the representative compound CEP significantly reduced viral load in the lungs and improved lung pathology in infected models. These findings highlight the potential of BBAs, particularly CEP, as promising candidates for the development of therapeutics against Influenza Virus infections.

Keywords

Bisbenzylisoquinoline alkaloids; Cepharanthine; Endosome; Influenza virus.

Figures
Products