Natural Binary Herbal Small Molecules Self-Assembled Nanogel for Synergistic Inhibition of Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is one of the most significant pathogenic infections in childhood, associated with high morbidity and mortality rates. Currently, there is no effective and safe drug or vaccine available for RSV. Glycyrrhizic acid (GA), an active compound derived from the natural he...

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Veröffentlicht in:ACS biomaterials science & engineering 2024-10, Vol.10 (10), p.6648-6660
Hauptverfasser: Song, Dandan, Lu, Chang, Chang, Chenqi, Ji, Jianjian, Lin, Lili, Liu, Yue, Li, Huizhu, Chen, Linwei, Chen, Zhipeng, Chen, Rui
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container_issue 10
container_start_page 6648
container_title ACS biomaterials science & engineering
container_volume 10
creator Song, Dandan
Lu, Chang
Chang, Chenqi
Ji, Jianjian
Lin, Lili
Liu, Yue
Li, Huizhu
Chen, Linwei
Chen, Zhipeng
Chen, Rui
description Respiratory syncytial virus (RSV) is one of the most significant pathogenic infections in childhood, associated with high morbidity and mortality rates. Currently, there is no effective and safe drug or vaccine available for RSV. Glycyrrhizic acid (GA), an active compound derived from the natural herb licorice, has been reported to provide protection against influenza and coronaviruses, exhibiting notable antiviral and anti-inflammatory properties. Ephedrine (EPH) is a commonly prescribed medication for the treatment of cough and asthma, and it also demonstrates certain antiviral effects. In this study, EPH and GA were combined to form an efficient nanomaterial (EPH-GA nanogel). The self-assembly of this nanogel is driven by hydrogen bonding and hydrophobic interactions, allowing it to serve as an antiviral nanomedicine without the need for a dual-component carrier, achieving a 100% drug loading efficiency. Oral administration of the EPH-GA nanogel significantly reduced viral load in the lungs of mice and improved lung lesions and tissue infiltration caused by RSV. Notably, we discovered that the assembled drug may create a “physical barrier” that prevents RSV from adsorbing to host cells, while free GA and EPH may compete with RSV for protein binding sites, thereby enhancing cellular uptake of EPH. Consequently, this prevents RSV infection and proliferation within host cells. Furthermore, the EC50 values changed from 310.83 μM for EPH and 262.88 μM for GA to 68.25 μM for the EPH-GA combination, with a combination index of 0.458. In addition, the in vivo biopharmaceutic process of GA and EPH was investigated, revealing that the oral administration of EPH-GA significantly increased the bioavailability of EPH while maintaining its plasma concentration at a relatively stable level. This enhancement may contribute to a synergistic antiviral effect when combined with GA. Furthermore, the in vivo process of EPH-GA demonstrates the advantage of delivering the drug to the lesion at elevated levels, thereby facilitating its antiviral mechanism at the cellular level. In this study, we identified an effective nanomedicine, EPH-GA nanogel, which can inhibit the proliferation of RSV and mitigate lung lesions resulting from viral infection by influencing the biopharmaceutical process in vivo. This research not only offers a novel strategy for the nanomedicine treatment of RSV but also elucidates, to some extent, the compatibility mechanisms of the multicomponents of tra
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Currently, there is no effective and safe drug or vaccine available for RSV. Glycyrrhizic acid (GA), an active compound derived from the natural herb licorice, has been reported to provide protection against influenza and coronaviruses, exhibiting notable antiviral and anti-inflammatory properties. Ephedrine (EPH) is a commonly prescribed medication for the treatment of cough and asthma, and it also demonstrates certain antiviral effects. In this study, EPH and GA were combined to form an efficient nanomaterial (EPH-GA nanogel). The self-assembly of this nanogel is driven by hydrogen bonding and hydrophobic interactions, allowing it to serve as an antiviral nanomedicine without the need for a dual-component carrier, achieving a 100% drug loading efficiency. Oral administration of the EPH-GA nanogel significantly reduced viral load in the lungs of mice and improved lung lesions and tissue infiltration caused by RSV. Notably, we discovered that the assembled drug may create a “physical barrier” that prevents RSV from adsorbing to host cells, while free GA and EPH may compete with RSV for protein binding sites, thereby enhancing cellular uptake of EPH. Consequently, this prevents RSV infection and proliferation within host cells. Furthermore, the EC50 values changed from 310.83 μM for EPH and 262.88 μM for GA to 68.25 μM for the EPH-GA combination, with a combination index of 0.458. In addition, the in vivo biopharmaceutic process of GA and EPH was investigated, revealing that the oral administration of EPH-GA significantly increased the bioavailability of EPH while maintaining its plasma concentration at a relatively stable level. This enhancement may contribute to a synergistic antiviral effect when combined with GA. Furthermore, the in vivo process of EPH-GA demonstrates the advantage of delivering the drug to the lesion at elevated levels, thereby facilitating its antiviral mechanism at the cellular level. In this study, we identified an effective nanomedicine, EPH-GA nanogel, which can inhibit the proliferation of RSV and mitigate lung lesions resulting from viral infection by influencing the biopharmaceutical process in vivo. This research not only offers a novel strategy for the nanomedicine treatment of RSV but also elucidates, to some extent, the compatibility mechanisms of the multicomponents of traditional Chinese medicine.</description><identifier>ISSN: 2373-9878</identifier><identifier>EISSN: 2373-9878</identifier><identifier>DOI: 10.1021/acsbiomaterials.4c01227</identifier><identifier>PMID: 39324477</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Antiviral Agents - administration &amp; dosage ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacokinetics ; Antiviral Agents - pharmacology ; Applications and Health ; Drug Synergism ; Female ; Glycyrrhizic Acid - chemistry ; Glycyrrhizic Acid - pharmacology ; Humans ; Lung - drug effects ; Lung - pathology ; Lung - virology ; Mice ; Mice, Inbred BALB C ; Nanogels - chemistry ; Polyethylene Glycols - chemistry ; Polyethylene Glycols - pharmacology ; Polyethyleneimine - chemistry ; Polyethyleneimine - pharmacology ; Respiratory Syncytial Virus Infections - drug therapy ; Respiratory Syncytial Virus Infections - virology ; Respiratory Syncytial Viruses - drug effects</subject><ispartof>ACS biomaterials science &amp; engineering, 2024-10, Vol.10 (10), p.6648-6660</ispartof><rights>2024 American Chemical Society</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a233t-d7d53c914a952cff38f8b69343639883f3bb7f69cc9386c6ebd9f075d9b9d61d3</cites><orcidid>0000-0002-8486-9007 ; 0000-0002-7702-5738 ; 0000-0003-0418-5236</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.4c01227$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsbiomaterials.4c01227$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27081,27929,27930,56743,56793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39324477$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Dandan</creatorcontrib><creatorcontrib>Lu, Chang</creatorcontrib><creatorcontrib>Chang, Chenqi</creatorcontrib><creatorcontrib>Ji, Jianjian</creatorcontrib><creatorcontrib>Lin, Lili</creatorcontrib><creatorcontrib>Liu, Yue</creatorcontrib><creatorcontrib>Li, Huizhu</creatorcontrib><creatorcontrib>Chen, Linwei</creatorcontrib><creatorcontrib>Chen, Zhipeng</creatorcontrib><creatorcontrib>Chen, Rui</creatorcontrib><title>Natural Binary Herbal Small Molecules Self-Assembled Nanogel for Synergistic Inhibition of Respiratory Syncytial Virus</title><title>ACS biomaterials science &amp; engineering</title><addtitle>ACS Biomater. Sci. Eng</addtitle><description>Respiratory syncytial virus (RSV) is one of the most significant pathogenic infections in childhood, associated with high morbidity and mortality rates. Currently, there is no effective and safe drug or vaccine available for RSV. Glycyrrhizic acid (GA), an active compound derived from the natural herb licorice, has been reported to provide protection against influenza and coronaviruses, exhibiting notable antiviral and anti-inflammatory properties. Ephedrine (EPH) is a commonly prescribed medication for the treatment of cough and asthma, and it also demonstrates certain antiviral effects. In this study, EPH and GA were combined to form an efficient nanomaterial (EPH-GA nanogel). The self-assembly of this nanogel is driven by hydrogen bonding and hydrophobic interactions, allowing it to serve as an antiviral nanomedicine without the need for a dual-component carrier, achieving a 100% drug loading efficiency. Oral administration of the EPH-GA nanogel significantly reduced viral load in the lungs of mice and improved lung lesions and tissue infiltration caused by RSV. Notably, we discovered that the assembled drug may create a “physical barrier” that prevents RSV from adsorbing to host cells, while free GA and EPH may compete with RSV for protein binding sites, thereby enhancing cellular uptake of EPH. Consequently, this prevents RSV infection and proliferation within host cells. Furthermore, the EC50 values changed from 310.83 μM for EPH and 262.88 μM for GA to 68.25 μM for the EPH-GA combination, with a combination index of 0.458. In addition, the in vivo biopharmaceutic process of GA and EPH was investigated, revealing that the oral administration of EPH-GA significantly increased the bioavailability of EPH while maintaining its plasma concentration at a relatively stable level. This enhancement may contribute to a synergistic antiviral effect when combined with GA. Furthermore, the in vivo process of EPH-GA demonstrates the advantage of delivering the drug to the lesion at elevated levels, thereby facilitating its antiviral mechanism at the cellular level. In this study, we identified an effective nanomedicine, EPH-GA nanogel, which can inhibit the proliferation of RSV and mitigate lung lesions resulting from viral infection by influencing the biopharmaceutical process in vivo. 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Sci. Eng</addtitle><date>2024-10-14</date><risdate>2024</risdate><volume>10</volume><issue>10</issue><spage>6648</spage><epage>6660</epage><pages>6648-6660</pages><issn>2373-9878</issn><eissn>2373-9878</eissn><abstract>Respiratory syncytial virus (RSV) is one of the most significant pathogenic infections in childhood, associated with high morbidity and mortality rates. Currently, there is no effective and safe drug or vaccine available for RSV. Glycyrrhizic acid (GA), an active compound derived from the natural herb licorice, has been reported to provide protection against influenza and coronaviruses, exhibiting notable antiviral and anti-inflammatory properties. Ephedrine (EPH) is a commonly prescribed medication for the treatment of cough and asthma, and it also demonstrates certain antiviral effects. In this study, EPH and GA were combined to form an efficient nanomaterial (EPH-GA nanogel). The self-assembly of this nanogel is driven by hydrogen bonding and hydrophobic interactions, allowing it to serve as an antiviral nanomedicine without the need for a dual-component carrier, achieving a 100% drug loading efficiency. Oral administration of the EPH-GA nanogel significantly reduced viral load in the lungs of mice and improved lung lesions and tissue infiltration caused by RSV. Notably, we discovered that the assembled drug may create a “physical barrier” that prevents RSV from adsorbing to host cells, while free GA and EPH may compete with RSV for protein binding sites, thereby enhancing cellular uptake of EPH. Consequently, this prevents RSV infection and proliferation within host cells. Furthermore, the EC50 values changed from 310.83 μM for EPH and 262.88 μM for GA to 68.25 μM for the EPH-GA combination, with a combination index of 0.458. In addition, the in vivo biopharmaceutic process of GA and EPH was investigated, revealing that the oral administration of EPH-GA significantly increased the bioavailability of EPH while maintaining its plasma concentration at a relatively stable level. This enhancement may contribute to a synergistic antiviral effect when combined with GA. Furthermore, the in vivo process of EPH-GA demonstrates the advantage of delivering the drug to the lesion at elevated levels, thereby facilitating its antiviral mechanism at the cellular level. In this study, we identified an effective nanomedicine, EPH-GA nanogel, which can inhibit the proliferation of RSV and mitigate lung lesions resulting from viral infection by influencing the biopharmaceutical process in vivo. This research not only offers a novel strategy for the nanomedicine treatment of RSV but also elucidates, to some extent, the compatibility mechanisms of the multicomponents of traditional Chinese medicine.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>39324477</pmid><doi>10.1021/acsbiomaterials.4c01227</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8486-9007</orcidid><orcidid>https://orcid.org/0000-0002-7702-5738</orcidid><orcidid>https://orcid.org/0000-0003-0418-5236</orcidid></addata></record>
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subjects Animals
Antiviral Agents - administration & dosage
Antiviral Agents - chemistry
Antiviral Agents - pharmacokinetics
Antiviral Agents - pharmacology
Applications and Health
Drug Synergism
Female
Glycyrrhizic Acid - chemistry
Glycyrrhizic Acid - pharmacology
Humans
Lung - drug effects
Lung - pathology
Lung - virology
Mice
Mice, Inbred BALB C
Nanogels - chemistry
Polyethylene Glycols - chemistry
Polyethylene Glycols - pharmacology
Polyethyleneimine - chemistry
Polyethyleneimine - pharmacology
Respiratory Syncytial Virus Infections - drug therapy
Respiratory Syncytial Virus Infections - virology
Respiratory Syncytial Viruses - drug effects
title Natural Binary Herbal Small Molecules Self-Assembled Nanogel for Synergistic Inhibition of Respiratory Syncytial Virus
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