Novel Sulfated Polysaccharides: Dissociation of Anti-Human Immunodeficiency Virus Activity from Antithrombin Activity
Novel sulfated polysaccharides, sulfated bacterial glycosaminoglycan (Org 31581) and chemically degraded heparin (Org 31733), have proved to bepotent and selective inhibitors ofhuman immunodeficiency virus (HIV)in vitro. Their 50% inhIbitory concentrations forHIV type 1 (HIV-1) in MT-4 cells were 0....
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| Veröffentlicht in: | The Journal of infectious diseases 1990-02, Vol.161 (2), p.208-213 |
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| creator | Baba, Masanori De Clercq, Erik Schols, Dominique Pauwels, Rudi Snoeck, Robert Van Boeckel, Constant Van Dedem, Gijs Kraaijeveld, Nelly Hobbelen, Paul Ottenheijm, Harry Den Hollander, Frank |
| description | Novel sulfated polysaccharides, sulfated bacterial glycosaminoglycan (Org 31581) and chemically degraded heparin (Org 31733), have proved to bepotent and selective inhibitors ofhuman immunodeficiency virus (HIV)in vitro. Their 50% inhIbitory concentrations forHIV type 1 (HIV-1) in MT-4 cells were 0.67 and 0.52 µ/ml, respectively. These values are comparable to those obtained for dextran sulfate and standard heparin (0.39 and 0.89 µ/ml, respectively). Org 31581 and Org 31733 showed much less antithrombin activity than did dextran sulfate and standard heparin. These results indicate that the anti-HIV activity ofsulfated polysaccharides can be dissociated from their antithrombin activity. Org 31581 and Org 31733 were equally inhibitory to HIV-2 and HIV-1 and were also inhibitory to the replication of human cytomegalovirus. Syncytium formation, induced by cocultivation of MOLT-4 (clone 8) cells with chronically HIV-1 infected HuT 78 cells, was also inhibited by Org 31581. As previously demonstrated with dextran sulfate and heparin, both Org 31581 and Org 31733 blocked virus adsorption to the host cells. These compounds offer great promise as candidate drugs for the chemotherapy of HIV infections. |
| doi_str_mv | 10.1093/infdis/161.2.208 |
| format | Article |
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Their 50% inhIbitory concentrations forHIV type 1 (HIV-1) in MT-4 cells were 0.67 and 0.52 µ/ml, respectively. These values are comparable to those obtained for dextran sulfate and standard heparin (0.39 and 0.89 µ/ml, respectively). Org 31581 and Org 31733 showed much less antithrombin activity than did dextran sulfate and standard heparin. These results indicate that the anti-HIV activity ofsulfated polysaccharides can be dissociated from their antithrombin activity. Org 31581 and Org 31733 were equally inhibitory to HIV-2 and HIV-1 and were also inhibitory to the replication of human cytomegalovirus. Syncytium formation, induced by cocultivation of MOLT-4 (clone 8) cells with chronically HIV-1 infected HuT 78 cells, was also inhibited by Org 31581. As previously demonstrated with dextran sulfate and heparin, both Org 31581 and Org 31733 blocked virus adsorption to the host cells. These compounds offer great promise as candidate drugs for the chemotherapy of HIV infections.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/161.2.208</identifier><identifier>PMID: 2405068</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>AIDS/HIV ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antithrombins ; Antiviral agents ; Biological and medical sciences ; Blood Coagulation - drug effects ; Cell Line ; Cell lines ; Dextrans ; Fibrinolytic Agents - pharmacology ; Fluorescent Antibody Technique ; Giant cells ; Glycosaminoglycans - pharmacology ; Heparin ; Heparin - pharmacology ; HIV ; HIV 1 ; HIV-1 - drug effects ; HIV-2 - drug effects ; Humans ; Major Articles ; Medical sciences ; Molecular Structure ; Pharmacology. Drug treatments ; Polysaccharides ; Sulfates ; Viruses</subject><ispartof>The Journal of infectious diseases, 1990-02, Vol.161 (2), p.208-213</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-364059a8b585b06b62f560dd21fc7dfaee47dcaded526621eaca8f25abb462d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30126077$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30126077$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19567148$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2405068$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baba, Masanori</creatorcontrib><creatorcontrib>De Clercq, Erik</creatorcontrib><creatorcontrib>Schols, Dominique</creatorcontrib><creatorcontrib>Pauwels, Rudi</creatorcontrib><creatorcontrib>Snoeck, Robert</creatorcontrib><creatorcontrib>Van Boeckel, Constant</creatorcontrib><creatorcontrib>Van Dedem, Gijs</creatorcontrib><creatorcontrib>Kraaijeveld, Nelly</creatorcontrib><creatorcontrib>Hobbelen, Paul</creatorcontrib><creatorcontrib>Ottenheijm, Harry</creatorcontrib><creatorcontrib>Den Hollander, Frank</creatorcontrib><title>Novel Sulfated Polysaccharides: Dissociation of Anti-Human Immunodeficiency Virus Activity from Antithrombin Activity</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Novel sulfated polysaccharides, sulfated bacterial glycosaminoglycan (Org 31581) and chemically degraded heparin (Org 31733), have proved to bepotent and selective inhibitors ofhuman immunodeficiency virus (HIV)in vitro. Their 50% inhIbitory concentrations forHIV type 1 (HIV-1) in MT-4 cells were 0.67 and 0.52 µ/ml, respectively. These values are comparable to those obtained for dextran sulfate and standard heparin (0.39 and 0.89 µ/ml, respectively). Org 31581 and Org 31733 showed much less antithrombin activity than did dextran sulfate and standard heparin. These results indicate that the anti-HIV activity ofsulfated polysaccharides can be dissociated from their antithrombin activity. Org 31581 and Org 31733 were equally inhibitory to HIV-2 and HIV-1 and were also inhibitory to the replication of human cytomegalovirus. Syncytium formation, induced by cocultivation of MOLT-4 (clone 8) cells with chronically HIV-1 infected HuT 78 cells, was also inhibited by Org 31581. As previously demonstrated with dextran sulfate and heparin, both Org 31581 and Org 31733 blocked virus adsorption to the host cells. These compounds offer great promise as candidate drugs for the chemotherapy of HIV infections.</description><subject>AIDS/HIV</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antithrombins</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Blood Coagulation - drug effects</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Dextrans</subject><subject>Fibrinolytic Agents - pharmacology</subject><subject>Fluorescent Antibody Technique</subject><subject>Giant cells</subject><subject>Glycosaminoglycans - pharmacology</subject><subject>Heparin</subject><subject>Heparin - pharmacology</subject><subject>HIV</subject><subject>HIV 1</subject><subject>HIV-1 - drug effects</subject><subject>HIV-2 - drug effects</subject><subject>Humans</subject><subject>Major Articles</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>Pharmacology. Drug treatments</subject><subject>Polysaccharides</subject><subject>Sulfates</subject><subject>Viruses</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rFTEUhoMo9ba6dyPMRndzm49JMuPu0qrTUqpikeImZPJBU2eSmmRK77837b0M7ro6B573PBx4AXiH4BrBjhw7b7VLx4ihNV5j2L4AK0QJrxlD5CVYQYhxjdquew0OU7qFEDaE8QNwgBtIIWtXYL4M92asfs6jldno6nsYt0kqdSOj0yZ9qk5dSkE5mV3wVbDVxmdX9_MkfXU2TbMP2linnPFqW_1ycU7VRmV37_K2sjFMT_l8U7bB-QW9Aa-sHJN5u59H4OrL56uTvr749vXsZHNRq4Z2uSasvNnJdqAtHSAbGLaUQa0xsoprK41puFZSG00xYxgZqWRrMZXD0DCsyRH4uNPexfB3NimLySVlxlF6E-YkeMdgQ9vu2SCiTcMpxyUId0EVQ0rRWHEX3STjViAoHhsRu0ZEaURgURopJ-_37nmYjF4O9hUU_mHPZVJytFF6VQSLt6OMo-Y_z23KIS6cQIQZ5LzwesddyuZh4TL-EYwTTkV__Vv86OF5f86vxSn5B9RNsPA</recordid><startdate>19900201</startdate><enddate>19900201</enddate><creator>Baba, Masanori</creator><creator>De Clercq, Erik</creator><creator>Schols, Dominique</creator><creator>Pauwels, Rudi</creator><creator>Snoeck, Robert</creator><creator>Van Boeckel, Constant</creator><creator>Van Dedem, Gijs</creator><creator>Kraaijeveld, Nelly</creator><creator>Hobbelen, Paul</creator><creator>Ottenheijm, Harry</creator><creator>Den Hollander, Frank</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><scope>BSCLL</scope><scope>IQODW</scope><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>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19900201</creationdate><title>Novel Sulfated Polysaccharides: Dissociation of Anti-Human Immunodeficiency Virus Activity from Antithrombin Activity</title><author>Baba, Masanori ; De Clercq, Erik ; Schols, Dominique ; Pauwels, Rudi ; Snoeck, Robert ; Van Boeckel, Constant ; Van Dedem, Gijs ; Kraaijeveld, Nelly ; Hobbelen, Paul ; Ottenheijm, Harry ; Den Hollander, Frank</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-364059a8b585b06b62f560dd21fc7dfaee47dcaded526621eaca8f25abb462d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>AIDS/HIV</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antithrombins</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Blood Coagulation - drug effects</topic><topic>Cell Line</topic><topic>Cell lines</topic><topic>Dextrans</topic><topic>Fibrinolytic Agents - pharmacology</topic><topic>Fluorescent Antibody Technique</topic><topic>Giant cells</topic><topic>Glycosaminoglycans - pharmacology</topic><topic>Heparin</topic><topic>Heparin - pharmacology</topic><topic>HIV</topic><topic>HIV 1</topic><topic>HIV-1 - drug effects</topic><topic>HIV-2 - drug effects</topic><topic>Humans</topic><topic>Major Articles</topic><topic>Medical sciences</topic><topic>Molecular Structure</topic><topic>Pharmacology. Drug treatments</topic><topic>Polysaccharides</topic><topic>Sulfates</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baba, Masanori</creatorcontrib><creatorcontrib>De Clercq, Erik</creatorcontrib><creatorcontrib>Schols, Dominique</creatorcontrib><creatorcontrib>Pauwels, Rudi</creatorcontrib><creatorcontrib>Snoeck, Robert</creatorcontrib><creatorcontrib>Van Boeckel, Constant</creatorcontrib><creatorcontrib>Van Dedem, Gijs</creatorcontrib><creatorcontrib>Kraaijeveld, Nelly</creatorcontrib><creatorcontrib>Hobbelen, Paul</creatorcontrib><creatorcontrib>Ottenheijm, Harry</creatorcontrib><creatorcontrib>Den Hollander, Frank</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</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>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baba, Masanori</au><au>De Clercq, Erik</au><au>Schols, Dominique</au><au>Pauwels, Rudi</au><au>Snoeck, Robert</au><au>Van Boeckel, Constant</au><au>Van Dedem, Gijs</au><au>Kraaijeveld, Nelly</au><au>Hobbelen, Paul</au><au>Ottenheijm, Harry</au><au>Den Hollander, Frank</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Sulfated Polysaccharides: Dissociation of Anti-Human Immunodeficiency Virus Activity from Antithrombin Activity</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>1990-02-01</date><risdate>1990</risdate><volume>161</volume><issue>2</issue><spage>208</spage><epage>213</epage><pages>208-213</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>Novel sulfated polysaccharides, sulfated bacterial glycosaminoglycan (Org 31581) and chemically degraded heparin (Org 31733), have proved to bepotent and selective inhibitors ofhuman immunodeficiency virus (HIV)in vitro. Their 50% inhIbitory concentrations forHIV type 1 (HIV-1) in MT-4 cells were 0.67 and 0.52 µ/ml, respectively. These values are comparable to those obtained for dextran sulfate and standard heparin (0.39 and 0.89 µ/ml, respectively). Org 31581 and Org 31733 showed much less antithrombin activity than did dextran sulfate and standard heparin. These results indicate that the anti-HIV activity ofsulfated polysaccharides can be dissociated from their antithrombin activity. Org 31581 and Org 31733 were equally inhibitory to HIV-2 and HIV-1 and were also inhibitory to the replication of human cytomegalovirus. Syncytium formation, induced by cocultivation of MOLT-4 (clone 8) cells with chronically HIV-1 infected HuT 78 cells, was also inhibited by Org 31581. As previously demonstrated with dextran sulfate and heparin, both Org 31581 and Org 31733 blocked virus adsorption to the host cells. These compounds offer great promise as candidate drugs for the chemotherapy of HIV infections.</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>2405068</pmid><doi>10.1093/infdis/161.2.208</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0022-1899 |
| ispartof | The Journal of infectious diseases, 1990-02, Vol.161 (2), p.208-213 |
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| language | eng |
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| subjects | AIDS/HIV Antibiotics. Antiinfectious agents. Antiparasitic agents Antithrombins Antiviral agents Biological and medical sciences Blood Coagulation - drug effects Cell Line Cell lines Dextrans Fibrinolytic Agents - pharmacology Fluorescent Antibody Technique Giant cells Glycosaminoglycans - pharmacology Heparin Heparin - pharmacology HIV HIV 1 HIV-1 - drug effects HIV-2 - drug effects Humans Major Articles Medical sciences Molecular Structure Pharmacology. Drug treatments Polysaccharides Sulfates Viruses |
| title | Novel Sulfated Polysaccharides: Dissociation of Anti-Human Immunodeficiency Virus Activity from Antithrombin Activity |
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