The Discovery of Potential IGF1R Inhibitors: A Combination of Virtual Screening, Molecular Docking Studies, and in vitro/in vivo Biological Evaluation

Abstract

Abstract Background Insulin-like growth factor 1 receptor (IGF1R) is a newly discovered key receptor that allows RSV to enter cells. RSV and IGF1R fusion triggers PKCζ activation, promoting cell signaling by recruiting nucleolin from the nucleus to the plasma membrane. It is tempting to speculate that other pneumoviruses, including bovine RSV, bind to the IGF1R. Methods Natural products that are effective against IGF1R protein were screened from TargetMol drugs datas by virtual screening. Virtual screening and in vivo and in vitro experiments were carried out. Results The results showed that Tannic acid and Daptomycin had anti-RSV potential through reducing viral loads, inflammation, airway resistance and protecting alveolar integrity. And the IC50 values of tannic acid and daptomycin were the 6 nM and 0.45 µM, respectively. Conclusions Novel small-molecule inhibitors targeting the IGF1R, Tannic acid or Daptomycin, may be effective anti-RSV therapy agents.