Diphyllin elicits a doubled-pronged attack on the entry of SARS-CoV-2 by inhibiting cathepsin L and furin
- Virus Res. 2024 Oct 19:350:199485. doi: 10.1016/j.virusres.2024.199485.
- 1. Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing 400016, China; Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
- 2. Institute for the Research on HIV and AIDS-associated Diseases, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany.
- 3. Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
- 4. Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing 400016, China; Department of Laboratory Medicine, Bishan Hospital of Chongqing Medical University, Chongqing 402760, China.
- 5. Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen 45239, Germany.
- 6. Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany.
- 7. Chongqing Yucai Secondary School, Chongqing 400050, China.
- 8. College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
- 9. Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
- 10. Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
- 11. Institute for the Research on HIV and AIDS-associated Diseases, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany. Electronic address: [email protected].
- 12. Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum Antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the Antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (S)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron. Accordingly, diphyllin also significantly inhibited the in vitro Infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease Cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing Furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and Furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.
-
Cat. No.Product NameDescriptionTargetResearch Area
-
-
Cat. No.Product NameCategory/Application