Screening and pharmacodynamic evaluation of the anti-respiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo.

Wang, Zhenya; Hou, Duoduo; Fang, Jieyu; Zhu, Li; Sun, Yingying; Tan, Yayun; Gu, Zichen; Shan, Lihong

Respiratory syncytial virus (RSV) causes serious lower respiratory tract infections and there are currently no safer or more effective drugs available. It is important to find novel medications for RSV infection. A series of steroidal pyridines was synthesized for screening and evaluation of their antiviral activity, and investigation of their antiviral mechanism of action. Compound 3l had the highest antiviral activity, with a half maximal effective concentration (EC50 ) of 3.13 μM. 3l was explored for its effects in vitro on RSV 2 hours before infection (pretreatment), at the time of infection (competition), and 2 hours after infection (postinfection). Toll-like receptor (TLR)-3, retinoic acid-inducible gene (RIG)-I, interleukin (IL)-6 and interferon (IFN)-β were suppressed at the cellular level. Mouse lung tissue was subjected to hematoxylin and eosin (HE) staining and immunohistochemistry, which showed that RSV antigen and M gene expression could be reduced by 3l. Decreased expression of TLR-3, RIG-I, IL-6, IFN-β and IL-10 was also found in vivo. The results indicated that compound 3l exerted its antiviral effects mainly through inhibition of viral replication and downregulation of inflammatory factors. This article is protected by copyright. All rights reserved.