2. Academic Validation
  3. Repurposing Axl Kinase Inhibitors for the Treatment of Respiratory Syncytial Virus Infection

Repurposing Axl Kinase Inhibitors for the Treatment of Respiratory Syncytial Virus Infection

  • Antimicrob Agents Chemother. 2023 Feb 28;e0148722. doi: 10.1128/aac.01487-22.
Dan Zhang 1 2,  Yuanhui Zhao 1 2 3,  Xiaoxin You 2,  Susu He 1 2 3,  Erguang Li 1 2 4 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, China.
  • 2 Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China.
  • 3 Yancheng Medical Research Center, The Affiliated Yancheng People's 1st Hospital of Nanjing University Medical School, Yancheng, Jiangsu, China.
  • 4 Institute of Medical Virology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
  • 5 Shenzhen Research Institute of Nanjing University, Shenzhen, China.
PMID: 36853000 DOI: 10.1128/aac.01487-22
Abstract

Respiratory syncytial virus (RSV) Infection persists as a common pathogen of pulmonary Infection in infants and in the elderly with high morbidity and mortality. However, no specific therapeutics are available. Axl, a member of the TAM (TYRO3, Axl, and Mertk) family receptor kinases, is a pleiotropic inhibitor of the innate immune response and functions as a negative regulator of interferon pathway activation. In this report, we investigated Axl inhibitors for their effects against RSV Infection. Axl inhibition with kinase inhibitors, including BMS-777607, R428, and TP-0903, or Axl ablation resulted in a significant reduction of RSV Infection in cell-based assays. In an animal model of pulmonary RSV Infection, treatment with BMS-777607, R428, or TP-0903 ameliorated pulmonary pathology with a significant reduction of RSV titers in the lung tissues and, consequently, decreased the expression of proinflammatory genes. The host promotes ISG expression for the Antiviral response and for viral clearance. We found that Axl inhibition led to more robust IFN-β expression and Antiviral gene induction. Thus, the results of this study imply that Axl kinase inhibitors may possess a broad spectrum of Antiviral effects by promoting ISG expression.

Keywords

Axl; IFN; RSV; antiviral; interferons; kinase inhibitor.

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