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Natural Product Kuwanon‐L Inhibits HIV‐1 Replication through Multiple Target Binding
In recent years many advances have been made in the fight against HIV‐1 infection. However, the lack of a vaccine, together with the increasing resistance to the highly active anti‐retroviral therapy (HAART), make HIV‐1 infection still a serious global emergency. Thus, new compounds with original mo...
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Published in: | Chembiochem : a European journal of chemical biology 2017-02, Vol.18 (4), p.374-377 |
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container_title | Chembiochem : a European journal of chemical biology |
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creator | Martini, Riccardo Esposito, Francesca Corona, Angela Ferrarese, Roberto Ceresola, Elisa Rita Visconti, Laura Tintori, Cristina Barbieri, Alessandro Calcaterra, Andrea Iovine, Valentina Canducci, Filippo Tramontano, Enzo Botta, Maurizio |
description | In recent years many advances have been made in the fight against HIV‐1 infection. However, the lack of a vaccine, together with the increasing resistance to the highly active anti‐retroviral therapy (HAART), make HIV‐1 infection still a serious global emergency. Thus, new compounds with original modes of action are continuously required, and natural products have ever been a very interesting class of pharmacologically active molecules. Some of them have been used since ancient times against viral infections. Here we present a work in which we suggest that kuwanon‐L, a natural product active as an HIV‐1 integrase (IN) inhibitor, might exert its overall antiviral activity through binding to multiple viral targets. Specific enzymatic tests, together with a time‐of‐addition (TOA) experiment, support our hypothesis of binding both to IN and to reverse transcriptase (RT). Overall, this compound can be considered an attractive lead for the development of new classes of antiviral agents able to overcome the problem of resistance, due to its ability to exert its action by binding simultaneously to multiple viral targets.
Two birds, one stone: We present an unusual time‐of‐addition profile for the natural compound kuwanon‐L (KUW), compatible with the inhibition of two key HIV‐1 enzymes: integrase (IN) and—unexpectedly—reverse transcriptase (RT). Enzymatic assays also showed anti‐RT activity, thus making kuwanon‐L a starting point for a multiple‐target‐binding strategy for potential application against HIV‐1. |
doi_str_mv | 10.1002/cbic.201600592 |
format | article |
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Two birds, one stone: We present an unusual time‐of‐addition profile for the natural compound kuwanon‐L (KUW), compatible with the inhibition of two key HIV‐1 enzymes: integrase (IN) and—unexpectedly—reverse transcriptase (RT). Enzymatic assays also showed anti‐RT activity, thus making kuwanon‐L a starting point for a multiple‐target‐binding strategy for potential application against HIV‐1.</description><identifier>ISSN: 1439-4227</identifier><identifier>EISSN: 1439-7633</identifier><identifier>DOI: 10.1002/cbic.201600592</identifier><identifier>PMID: 27992102</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Anti-HIV Agents - chemistry ; Anti-HIV Agents - pharmacology ; antiviral agents ; Cell Line ; Drug Delivery Systems ; Flavonolignans - chemistry ; Flavonolignans - pharmacology ; HIV-1 - drug effects ; HIV-1 RNase H ; Humans ; inhibitors ; kuwanon-L ; Lentivirus ; Molecular Structure ; multiple target binding ; Natural products ; Viral infections ; Virus Replication - drug effects</subject><ispartof>Chembiochem : a European journal of chemical biology, 2017-02, Vol.18 (4), p.374-377</ispartof><rights>2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4432-601c23a018a8d64cf2f5f4b116827c8dea3fd02985a45e2b1419aa184d367c683</citedby><cites>FETCH-LOGICAL-c4432-601c23a018a8d64cf2f5f4b116827c8dea3fd02985a45e2b1419aa184d367c683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27992102$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martini, Riccardo</creatorcontrib><creatorcontrib>Esposito, Francesca</creatorcontrib><creatorcontrib>Corona, Angela</creatorcontrib><creatorcontrib>Ferrarese, Roberto</creatorcontrib><creatorcontrib>Ceresola, Elisa Rita</creatorcontrib><creatorcontrib>Visconti, Laura</creatorcontrib><creatorcontrib>Tintori, Cristina</creatorcontrib><creatorcontrib>Barbieri, Alessandro</creatorcontrib><creatorcontrib>Calcaterra, Andrea</creatorcontrib><creatorcontrib>Iovine, Valentina</creatorcontrib><creatorcontrib>Canducci, Filippo</creatorcontrib><creatorcontrib>Tramontano, Enzo</creatorcontrib><creatorcontrib>Botta, Maurizio</creatorcontrib><title>Natural Product Kuwanon‐L Inhibits HIV‐1 Replication through Multiple Target Binding</title><title>Chembiochem : a European journal of chemical biology</title><addtitle>Chembiochem</addtitle><description>In recent years many advances have been made in the fight against HIV‐1 infection. However, the lack of a vaccine, together with the increasing resistance to the highly active anti‐retroviral therapy (HAART), make HIV‐1 infection still a serious global emergency. Thus, new compounds with original modes of action are continuously required, and natural products have ever been a very interesting class of pharmacologically active molecules. Some of them have been used since ancient times against viral infections. Here we present a work in which we suggest that kuwanon‐L, a natural product active as an HIV‐1 integrase (IN) inhibitor, might exert its overall antiviral activity through binding to multiple viral targets. Specific enzymatic tests, together with a time‐of‐addition (TOA) experiment, support our hypothesis of binding both to IN and to reverse transcriptase (RT). Overall, this compound can be considered an attractive lead for the development of new classes of antiviral agents able to overcome the problem of resistance, due to its ability to exert its action by binding simultaneously to multiple viral targets.
Two birds, one stone: We present an unusual time‐of‐addition profile for the natural compound kuwanon‐L (KUW), compatible with the inhibition of two key HIV‐1 enzymes: integrase (IN) and—unexpectedly—reverse transcriptase (RT). Enzymatic assays also showed anti‐RT activity, thus making kuwanon‐L a starting point for a multiple‐target‐binding strategy for potential application against HIV‐1.</description><subject>Anti-HIV Agents - chemistry</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>antiviral agents</subject><subject>Cell Line</subject><subject>Drug Delivery Systems</subject><subject>Flavonolignans - chemistry</subject><subject>Flavonolignans - pharmacology</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 RNase H</subject><subject>Humans</subject><subject>inhibitors</subject><subject>kuwanon-L</subject><subject>Lentivirus</subject><subject>Molecular Structure</subject><subject>multiple target binding</subject><subject>Natural products</subject><subject>Viral infections</subject><subject>Virus Replication - drug effects</subject><issn>1439-4227</issn><issn>1439-7633</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqN0ctOGzEUBmCrasUlsO2yssSGTVIf2-PLskS0RIQWoYC6G3k8nsRoMhPssRA7HoFn5EmYKIFKbKi8sGV955eOfoS-AhkBIfS7LbwdUQKCkEzTT2gPONNDKRj7vH1zSuUu2o_xlhCiBYMdtEul1hQI3UN_f5suBVPjy9CWyXb4PN2bpm2eH5-meNIsfOG7iM8mN_0H4Cu3qr01nW8b3C1Cm-YLfJHqzq9qh2cmzF2HT3xT-mZ-gL5Upo7ucHsP0PXP09n4bDj982sy_jEdWs4ZHQoCljJDQBlVCm4rWmUVLwCEotKq0hlWlYRqlRmeOVoAB20MKF4yIa1QbICON7mr0N4lF7t86aN1dW0a16aYg5JUcSAS_oNmQJVWkvX06B29bVNo-kV6JfojiVir0UbZ0MYYXJWvgl-a8JADydf15Ot68rd6-oFv29hULF35xl_76IHegHtfu4cP4vLxyWT8L_wF1J6bdg</recordid><startdate>20170216</startdate><enddate>20170216</enddate><creator>Martini, Riccardo</creator><creator>Esposito, Francesca</creator><creator>Corona, Angela</creator><creator>Ferrarese, Roberto</creator><creator>Ceresola, Elisa Rita</creator><creator>Visconti, Laura</creator><creator>Tintori, Cristina</creator><creator>Barbieri, Alessandro</creator><creator>Calcaterra, Andrea</creator><creator>Iovine, Valentina</creator><creator>Canducci, Filippo</creator><creator>Tramontano, Enzo</creator><creator>Botta, Maurizio</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7TM</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>7X8</scope></search><sort><creationdate>20170216</creationdate><title>Natural Product Kuwanon‐L Inhibits HIV‐1 Replication through Multiple Target Binding</title><author>Martini, Riccardo ; Esposito, Francesca ; Corona, Angela ; Ferrarese, Roberto ; Ceresola, Elisa Rita ; Visconti, Laura ; Tintori, Cristina ; Barbieri, Alessandro ; Calcaterra, Andrea ; Iovine, Valentina ; Canducci, Filippo ; Tramontano, Enzo ; Botta, Maurizio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4432-601c23a018a8d64cf2f5f4b116827c8dea3fd02985a45e2b1419aa184d367c683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Anti-HIV Agents - chemistry</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>antiviral agents</topic><topic>Cell Line</topic><topic>Drug Delivery Systems</topic><topic>Flavonolignans - chemistry</topic><topic>Flavonolignans - pharmacology</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 RNase H</topic><topic>Humans</topic><topic>inhibitors</topic><topic>kuwanon-L</topic><topic>Lentivirus</topic><topic>Molecular Structure</topic><topic>multiple target binding</topic><topic>Natural products</topic><topic>Viral infections</topic><topic>Virus Replication - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martini, Riccardo</creatorcontrib><creatorcontrib>Esposito, Francesca</creatorcontrib><creatorcontrib>Corona, Angela</creatorcontrib><creatorcontrib>Ferrarese, Roberto</creatorcontrib><creatorcontrib>Ceresola, Elisa Rita</creatorcontrib><creatorcontrib>Visconti, Laura</creatorcontrib><creatorcontrib>Tintori, Cristina</creatorcontrib><creatorcontrib>Barbieri, Alessandro</creatorcontrib><creatorcontrib>Calcaterra, Andrea</creatorcontrib><creatorcontrib>Iovine, Valentina</creatorcontrib><creatorcontrib>Canducci, Filippo</creatorcontrib><creatorcontrib>Tramontano, Enzo</creatorcontrib><creatorcontrib>Botta, Maurizio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids 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>MEDLINE - Academic</collection><jtitle>Chembiochem : a European journal of chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martini, Riccardo</au><au>Esposito, Francesca</au><au>Corona, Angela</au><au>Ferrarese, Roberto</au><au>Ceresola, Elisa Rita</au><au>Visconti, Laura</au><au>Tintori, Cristina</au><au>Barbieri, Alessandro</au><au>Calcaterra, Andrea</au><au>Iovine, Valentina</au><au>Canducci, Filippo</au><au>Tramontano, Enzo</au><au>Botta, Maurizio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Natural Product Kuwanon‐L Inhibits HIV‐1 Replication through Multiple Target Binding</atitle><jtitle>Chembiochem : a European journal of chemical biology</jtitle><addtitle>Chembiochem</addtitle><date>2017-02-16</date><risdate>2017</risdate><volume>18</volume><issue>4</issue><spage>374</spage><epage>377</epage><pages>374-377</pages><issn>1439-4227</issn><eissn>1439-7633</eissn><abstract>In recent years many advances have been made in the fight against HIV‐1 infection. However, the lack of a vaccine, together with the increasing resistance to the highly active anti‐retroviral therapy (HAART), make HIV‐1 infection still a serious global emergency. Thus, new compounds with original modes of action are continuously required, and natural products have ever been a very interesting class of pharmacologically active molecules. Some of them have been used since ancient times against viral infections. Here we present a work in which we suggest that kuwanon‐L, a natural product active as an HIV‐1 integrase (IN) inhibitor, might exert its overall antiviral activity through binding to multiple viral targets. Specific enzymatic tests, together with a time‐of‐addition (TOA) experiment, support our hypothesis of binding both to IN and to reverse transcriptase (RT). Overall, this compound can be considered an attractive lead for the development of new classes of antiviral agents able to overcome the problem of resistance, due to its ability to exert its action by binding simultaneously to multiple viral targets.
Two birds, one stone: We present an unusual time‐of‐addition profile for the natural compound kuwanon‐L (KUW), compatible with the inhibition of two key HIV‐1 enzymes: integrase (IN) and—unexpectedly—reverse transcriptase (RT). Enzymatic assays also showed anti‐RT activity, thus making kuwanon‐L a starting point for a multiple‐target‐binding strategy for potential application against HIV‐1.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>27992102</pmid><doi>10.1002/cbic.201600592</doi><tpages>4</tpages></addata></record> |
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subjects | Anti-HIV Agents - chemistry Anti-HIV Agents - pharmacology antiviral agents Cell Line Drug Delivery Systems Flavonolignans - chemistry Flavonolignans - pharmacology HIV-1 - drug effects HIV-1 RNase H Humans inhibitors kuwanon-L Lentivirus Molecular Structure multiple target binding Natural products Viral infections Virus Replication - drug effects |
title | Natural Product Kuwanon‐L Inhibits HIV‐1 Replication through Multiple Target Binding |
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