Emodin inhibits respiratory syncytial virus entry by interactions with fusion protein

  • Front Microbiol. 2024 May 16:15:1393511. doi: 10.3389/fmicb.2024.1393511.
Yingcai Xiong  #  1  2  3 Guangxing Tan  #  1 Keyu Tao  #  2  3 Yinghui Zhou  3 Jun Li  2 Weiying Ou  3 Cunsi Shen  3 Tong Xie  3 Chao Zhang  2 Yayi Hou  4 Jianjian Ji  3
Affiliations
  • 1. Wuxi Traditional Chinese Medicine Hospial Afiliated to Nanjing University of Chinese Medicine, Wuxi 214071, China.
  • 2. School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • 3. Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China.
  • 4. The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
  • # Contributed equally.
Abstract

Introduction: Respiratory syncytial virus (RSV) fusion (F) protein is essential for facilitating virus entry into host cells, providing a hopeful path for combating viral diseases. However, F protein inhibitors can rapidly select for viral resistance. Thus, discovering new inhibitors of F-protein is necessary to enrich the RSV drug development pipeline.

Methods: In this study, we screen 25 bioactive compounds from Chinese herbal medicines that exhibit a strong binding to the RSV-F protein using surface plasmon resonance.

Results: After screening, we found emodin could strongly bind to RSV-F protein, and could effectively curb RSV Infection. Further investigations certificated that emodin specifically disrupts the attachment and internalization phases of RSV Infection by targeting the RSV-F protein. In vivo studies with mice infected with RSV demonstrated that emodin effectively reduces lung pathology. This therapeutic effect is attributed to emodin's capacity to diminish pro-inflammatory cytokine production and reduce viral load in the lungs.

Discussion: In conclusion, our findings provide initial insights into the mechanism by which emodin counters RSV Infection via engagement with the RSV-F protein, establishing it as a viable contender for the development of novel therapeutic agents aimed at RSV.

Keywords
emodin; entry; fusion protein; respiratory syncytial virus; small molecule inhibitor.
Products
Inhibitors & Agonists
Other Products