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Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo
Author(s) -
Wang Zhenya,
Hou Duoduo,
Fang Jieyu,
Zhu Li,
Sun Yingying,
Tan Yayun,
Gu Zichen,
Shan Lihong
Publication year - 2021
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.26604
Subject(s) - in vivo , virus , in vitro , virology , biology , interferon , antiviral drug , pharmacology , biochemistry , microbiology and biotechnology
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 were 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 (EC 50 ) of 3.13 μM. Compound 3l was explored for its effects in vitro on RSV 2 h before infection (pretreatment), at the time of infection (competition), and 2 h 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 compound 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.