Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo
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...
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| Veröffentlicht in: | Journal of medical virology 2021-06, Vol.93 (6), p.3428-3438 |
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| creator | Wang, Zhenya Hou, Duoduo Fang, Jieyu Zhu, Li Sun, Yingying Tan, Yayun Gu, Zichen Shan, Lihong |
| description | 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 (EC50) 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. |
| doi_str_mv | 10.1002/jmv.26604 |
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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 (EC50) 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.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.26604</identifier><identifier>PMID: 33064304</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animal tissues ; Antigens ; Antiviral activity ; Antiviral agents ; Gene expression ; Immunohistochemistry ; Infections ; Inflammation ; inflammatory factor ; Interferon ; Interleukins ; M gene ; Pharmacodynamics ; Pyridines ; Respiratory syncytial virus ; Respiratory tract ; Respiratory tract diseases ; Retinoic acid ; Screening ; steroidal pyridines ; Toll-like receptors ; Virology ; Viruses</subject><ispartof>Journal of medical virology, 2021-06, Vol.93 (6), p.3428-3438</ispartof><rights>2020 Wiley Periodicals LLC</rights><rights>2020 Wiley Periodicals LLC.</rights><rights>2021 Wiley Periodicals LLC</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3534-22a73342f855c933fcf08c23e85ba1b21ed85f02d8388476037d509f40ced5a53</citedby><cites>FETCH-LOGICAL-c3534-22a73342f855c933fcf08c23e85ba1b21ed85f02d8388476037d509f40ced5a53</cites><orcidid>0000-0002-5314-6156</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.26604$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.26604$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33064304$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Zhenya</creatorcontrib><creatorcontrib>Hou, Duoduo</creatorcontrib><creatorcontrib>Fang, Jieyu</creatorcontrib><creatorcontrib>Zhu, Li</creatorcontrib><creatorcontrib>Sun, Yingying</creatorcontrib><creatorcontrib>Tan, Yayun</creatorcontrib><creatorcontrib>Gu, Zichen</creatorcontrib><creatorcontrib>Shan, Lihong</creatorcontrib><title>Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo</title><title>Journal of medical virology</title><addtitle>J Med Virol</addtitle><description>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 (EC50) 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.</description><subject>Animal tissues</subject><subject>Antigens</subject><subject>Antiviral activity</subject><subject>Antiviral agents</subject><subject>Gene expression</subject><subject>Immunohistochemistry</subject><subject>Infections</subject><subject>Inflammation</subject><subject>inflammatory factor</subject><subject>Interferon</subject><subject>Interleukins</subject><subject>M gene</subject><subject>Pharmacodynamics</subject><subject>Pyridines</subject><subject>Respiratory syncytial virus</subject><subject>Respiratory tract</subject><subject>Respiratory tract diseases</subject><subject>Retinoic acid</subject><subject>Screening</subject><subject>steroidal pyridines</subject><subject>Toll-like receptors</subject><subject>Virology</subject><subject>Viruses</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp10ctu1DAUBmALgehQWPACyBIbWKQ9viXOElVcVcSCy9by2A71KLGD7QTlIXhn3JnCAomVdeTP_7H0I_SUwAUBoJeHab2gbQv8HtoR6Numh47cRzsgvG3alogz9CjnAwDIntKH6IwxaDkDvkO_PpvkXPDhO9bB4vlGp0mbaLegJ2-wW_W46OJjwHHA5cZVVXxyefZJl5g2nLdgtuL1iFefloy1KX71Zbv1ubgUva1385a89cFhE6c5LsFm7EN9UVI87j0Oa3yMHgx6zO7J3XmOvr55_eXqXXP96e37q1fXjWGC8YZS3THG6SCFMD1jgxlAGsqcFHtN9pQ4K8UA1EomJe9aYJ0V0A8cjLNCC3aOXpxy5xR_LC4XNfls3Djq4OKSFeWCSNGzjlf6_B96iEsK9XeKCkIk5x1rq3p5UibFnJMb1Jz8pNOmCKjbjlTtSB07qvbZXeKyn5z9K_-UUsHlCfz0o9v-n6Q-fPx2ivwNTW2dmg</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Wang, Zhenya</creator><creator>Hou, Duoduo</creator><creator>Fang, Jieyu</creator><creator>Zhu, Li</creator><creator>Sun, Yingying</creator><creator>Tan, Yayun</creator><creator>Gu, Zichen</creator><creator>Shan, Lihong</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5314-6156</orcidid></search><sort><creationdate>202106</creationdate><title>Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo</title><author>Wang, Zhenya ; Hou, Duoduo ; Fang, Jieyu ; Zhu, Li ; Sun, Yingying ; Tan, Yayun ; Gu, Zichen ; Shan, Lihong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3534-22a73342f855c933fcf08c23e85ba1b21ed85f02d8388476037d509f40ced5a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animal tissues</topic><topic>Antigens</topic><topic>Antiviral activity</topic><topic>Antiviral agents</topic><topic>Gene expression</topic><topic>Immunohistochemistry</topic><topic>Infections</topic><topic>Inflammation</topic><topic>inflammatory factor</topic><topic>Interferon</topic><topic>Interleukins</topic><topic>M gene</topic><topic>Pharmacodynamics</topic><topic>Pyridines</topic><topic>Respiratory syncytial virus</topic><topic>Respiratory tract</topic><topic>Respiratory tract diseases</topic><topic>Retinoic acid</topic><topic>Screening</topic><topic>steroidal pyridines</topic><topic>Toll-like receptors</topic><topic>Virology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Zhenya</creatorcontrib><creatorcontrib>Hou, Duoduo</creatorcontrib><creatorcontrib>Fang, Jieyu</creatorcontrib><creatorcontrib>Zhu, Li</creatorcontrib><creatorcontrib>Sun, Yingying</creatorcontrib><creatorcontrib>Tan, Yayun</creatorcontrib><creatorcontrib>Gu, Zichen</creatorcontrib><creatorcontrib>Shan, Lihong</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Zhenya</au><au>Hou, Duoduo</au><au>Fang, Jieyu</au><au>Zhu, Li</au><au>Sun, Yingying</au><au>Tan, Yayun</au><au>Gu, Zichen</au><au>Shan, Lihong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J Med Virol</addtitle><date>2021-06</date><risdate>2021</risdate><volume>93</volume><issue>6</issue><spage>3428</spage><epage>3438</epage><pages>3428-3438</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><abstract>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 (EC50) 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. 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| subjects | Animal tissues Antigens Antiviral activity Antiviral agents Gene expression Immunohistochemistry Infections Inflammation inflammatory factor Interferon Interleukins M gene Pharmacodynamics Pyridines Respiratory syncytial virus Respiratory tract Respiratory tract diseases Retinoic acid Screening steroidal pyridines Toll-like receptors Virology Viruses |
| title | Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo |
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