GSK983: A novel compound with broad-spectrum antiviral activity
GSK983, a novel tetrahydrocarbazole, inhibits the replication of a variety of unrelated viruses in vitro with EC 50 values of 5–20 nM. Both replication of the adenovirus Ad-5 and the polyoma virus SV-40, and episomal maintenance of human papillomaviruses (HPV) and Epstein-Barr virus (EBV) are suscep...
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| Veröffentlicht in: | Antiviral research 2009-04, Vol.82 (1), p.1-11 |
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| creator | Harvey, Robert Brown, Kevin Zhang, Qin Gartland, Margaret Walton, Leslie Talarico, Christine Lawrence, Wendell Selleseth, Dean Coffield, Neil Leary, Jeffry Moniri, Kelly Singer, Sara Strum, Jay Gudmundsson, Kristjan Biron, Karen Romines, Karen R. Sethna, Phiroze |
| description | GSK983, a novel tetrahydrocarbazole, inhibits the replication of a variety of unrelated viruses in vitro with EC
50 values of 5–20
nM. Both replication of the adenovirus Ad-5 and the polyoma virus SV-40, and episomal maintenance of human papillomaviruses (HPV) and Epstein-Barr virus (EBV) are susceptible to GSK983. The compound does not inhibit all viruses; herpes simplex virus (HSV-1), human immunodeficiency virus (HIV), and lytic replication of EBV were not susceptible at concentrations below 1
μM. GSK983 does inhibit the growth of cell lines immortalized by HTLV-1, EBV, HPV, SV40 and Ad-5, with EC
50 values in the range of 10–40
nM. Depending on the cell line, the compound induces either apoptosis or cytostasis at concentrations over 20
nM. GSK983 also inhibits cell lines immortalized by non-viral mechanisms, but has little effect on primary cells. The CC
50 values for keratinocytes, fibroblasts, lymphocytes, endothelial, and bone marrow progenitor cells are all above 10
μM. The pattern of inhibition, which includes diverse viruses as well as growth of immortalized cells of varied origins, suggests the target is a host cell protein, rather than a viral protein. Preliminary mechanism studies indicate that GSK983 acts by inducing a subset of interferon-stimulated genes. |
| doi_str_mv | 10.1016/j.antiviral.2008.12.015 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7114156</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0166354209000163</els_id><sourcerecordid>20433853</sourcerecordid><originalsourceid>FETCH-LOGICAL-c534t-b8918733eab85f58539a8b3fc4463c8a5d54fdc3f2fb78327e845cf241c0e1fe3</originalsourceid><addsrcrecordid>eNqFkV9P2zAUxa1paC1sX2HkZXtL8N_E2cOmCkFBVOJh8Gw5zjW4SuLOTor49rhq1W1PPNmSf_ecc48ROie4IJiUF-tCD6PbuqC7gmIsC0ILTMQHNCeyonmN6_IjmieyzJngdIZOY1xjjMuqlp_QjNQJq2o2R7-Wv-9qyX5ki2zwW-gy4_uNn4Y2e3Hjc9YEr9s8bsCMYeqzo2mmze42vn5GJ1Z3Eb4czjP0eH31cHmTr-6Xt5eLVW4E42PeyJ0jY6AbKayQgtVaNswazktmpBat4LY1zFLbVJLRCiQXxlJODAZigZ2hn3vdzdT00BoYxhRDbYLrdXhVXjv1_8vgntWT36qKEE5EmQS-HwSC_zNBHFXvooGu0wP4KSqKOWMpVwKrPWiCjzGAPZoQrHblq7U69qB25StCVSo_TX79N-PfuUPbCfh2AHQ0urNBD8bFI0cJS7uXMnGLPQep0a2DoKJxMBhoXUg_oVrv3g3zBn5nqB0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20433853</pqid></control><display><type>article</type><title>GSK983: A novel compound with broad-spectrum antiviral activity</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Harvey, Robert ; Brown, Kevin ; Zhang, Qin ; Gartland, Margaret ; Walton, Leslie ; Talarico, Christine ; Lawrence, Wendell ; Selleseth, Dean ; Coffield, Neil ; Leary, Jeffry ; Moniri, Kelly ; Singer, Sara ; Strum, Jay ; Gudmundsson, Kristjan ; Biron, Karen ; Romines, Karen R. ; Sethna, Phiroze</creator><creatorcontrib>Harvey, Robert ; Brown, Kevin ; Zhang, Qin ; Gartland, Margaret ; Walton, Leslie ; Talarico, Christine ; Lawrence, Wendell ; Selleseth, Dean ; Coffield, Neil ; Leary, Jeffry ; Moniri, Kelly ; Singer, Sara ; Strum, Jay ; Gudmundsson, Kristjan ; Biron, Karen ; Romines, Karen R. ; Sethna, Phiroze</creatorcontrib><description>GSK983, a novel tetrahydrocarbazole, inhibits the replication of a variety of unrelated viruses in vitro with EC
50 values of 5–20
nM. Both replication of the adenovirus Ad-5 and the polyoma virus SV-40, and episomal maintenance of human papillomaviruses (HPV) and Epstein-Barr virus (EBV) are susceptible to GSK983. The compound does not inhibit all viruses; herpes simplex virus (HSV-1), human immunodeficiency virus (HIV), and lytic replication of EBV were not susceptible at concentrations below 1
μM. GSK983 does inhibit the growth of cell lines immortalized by HTLV-1, EBV, HPV, SV40 and Ad-5, with EC
50 values in the range of 10–40
nM. Depending on the cell line, the compound induces either apoptosis or cytostasis at concentrations over 20
nM. GSK983 also inhibits cell lines immortalized by non-viral mechanisms, but has little effect on primary cells. The CC
50 values for keratinocytes, fibroblasts, lymphocytes, endothelial, and bone marrow progenitor cells are all above 10
μM. The pattern of inhibition, which includes diverse viruses as well as growth of immortalized cells of varied origins, suggests the target is a host cell protein, rather than a viral protein. Preliminary mechanism studies indicate that GSK983 acts by inducing a subset of interferon-stimulated genes.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2008.12.015</identifier><identifier>PMID: 19187793</identifier><identifier>CODEN: ARSRDR</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>Adenovirus ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Antiviral Agents - pharmacology ; Apoptosis - drug effects ; Biological and medical sciences ; Carbazoles - pharmacology ; Cell Line, Transformed ; Cell Transformation, Viral ; Cells, Cultured ; DNA Viruses - drug effects ; DNA Viruses - physiology ; Epstein-Barr virus ; GSK983 ; Herpes simplex virus 1 ; Human immunodeficiency virus ; Human papillomavirus ; Human T-lymphotropic virus 1 ; Humans ; Interferon-stimulated genes ; Medical sciences ; Novel antiviral ; Pharmacology. Drug treatments ; Polyomavirus ; Simian virus 40 ; Tetrahydrocarbazole ; Virus Replication - drug effects</subject><ispartof>Antiviral research, 2009-04, Vol.82 (1), p.1-11</ispartof><rights>2009 Elsevier B.V.</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009 Elsevier B.V. All rights reserved. 2009 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-b8918733eab85f58539a8b3fc4463c8a5d54fdc3f2fb78327e845cf241c0e1fe3</citedby><cites>FETCH-LOGICAL-c534t-b8918733eab85f58539a8b3fc4463c8a5d54fdc3f2fb78327e845cf241c0e1fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0166354209000163$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21378368$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19187793$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harvey, Robert</creatorcontrib><creatorcontrib>Brown, Kevin</creatorcontrib><creatorcontrib>Zhang, Qin</creatorcontrib><creatorcontrib>Gartland, Margaret</creatorcontrib><creatorcontrib>Walton, Leslie</creatorcontrib><creatorcontrib>Talarico, Christine</creatorcontrib><creatorcontrib>Lawrence, Wendell</creatorcontrib><creatorcontrib>Selleseth, Dean</creatorcontrib><creatorcontrib>Coffield, Neil</creatorcontrib><creatorcontrib>Leary, Jeffry</creatorcontrib><creatorcontrib>Moniri, Kelly</creatorcontrib><creatorcontrib>Singer, Sara</creatorcontrib><creatorcontrib>Strum, Jay</creatorcontrib><creatorcontrib>Gudmundsson, Kristjan</creatorcontrib><creatorcontrib>Biron, Karen</creatorcontrib><creatorcontrib>Romines, Karen R.</creatorcontrib><creatorcontrib>Sethna, Phiroze</creatorcontrib><title>GSK983: A novel compound with broad-spectrum antiviral activity</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>GSK983, a novel tetrahydrocarbazole, inhibits the replication of a variety of unrelated viruses in vitro with EC
50 values of 5–20
nM. Both replication of the adenovirus Ad-5 and the polyoma virus SV-40, and episomal maintenance of human papillomaviruses (HPV) and Epstein-Barr virus (EBV) are susceptible to GSK983. The compound does not inhibit all viruses; herpes simplex virus (HSV-1), human immunodeficiency virus (HIV), and lytic replication of EBV were not susceptible at concentrations below 1
μM. GSK983 does inhibit the growth of cell lines immortalized by HTLV-1, EBV, HPV, SV40 and Ad-5, with EC
50 values in the range of 10–40
nM. Depending on the cell line, the compound induces either apoptosis or cytostasis at concentrations over 20
nM. GSK983 also inhibits cell lines immortalized by non-viral mechanisms, but has little effect on primary cells. The CC
50 values for keratinocytes, fibroblasts, lymphocytes, endothelial, and bone marrow progenitor cells are all above 10
μM. The pattern of inhibition, which includes diverse viruses as well as growth of immortalized cells of varied origins, suggests the target is a host cell protein, rather than a viral protein. Preliminary mechanism studies indicate that GSK983 acts by inducing a subset of interferon-stimulated genes.</description><subject>Adenovirus</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Carbazoles - pharmacology</subject><subject>Cell Line, Transformed</subject><subject>Cell Transformation, Viral</subject><subject>Cells, Cultured</subject><subject>DNA Viruses - drug effects</subject><subject>DNA Viruses - physiology</subject><subject>Epstein-Barr virus</subject><subject>GSK983</subject><subject>Herpes simplex virus 1</subject><subject>Human immunodeficiency virus</subject><subject>Human papillomavirus</subject><subject>Human T-lymphotropic virus 1</subject><subject>Humans</subject><subject>Interferon-stimulated genes</subject><subject>Medical sciences</subject><subject>Novel antiviral</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyomavirus</subject><subject>Simian virus 40</subject><subject>Tetrahydrocarbazole</subject><subject>Virus Replication - drug effects</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV9P2zAUxa1paC1sX2HkZXtL8N_E2cOmCkFBVOJh8Gw5zjW4SuLOTor49rhq1W1PPNmSf_ecc48ROie4IJiUF-tCD6PbuqC7gmIsC0ILTMQHNCeyonmN6_IjmieyzJngdIZOY1xjjMuqlp_QjNQJq2o2R7-Wv-9qyX5ki2zwW-gy4_uNn4Y2e3Hjc9YEr9s8bsCMYeqzo2mmze42vn5GJ1Z3Eb4czjP0eH31cHmTr-6Xt5eLVW4E42PeyJ0jY6AbKayQgtVaNswazktmpBat4LY1zFLbVJLRCiQXxlJODAZigZ2hn3vdzdT00BoYxhRDbYLrdXhVXjv1_8vgntWT36qKEE5EmQS-HwSC_zNBHFXvooGu0wP4KSqKOWMpVwKrPWiCjzGAPZoQrHblq7U69qB25StCVSo_TX79N-PfuUPbCfh2AHQ0urNBD8bFI0cJS7uXMnGLPQep0a2DoKJxMBhoXUg_oVrv3g3zBn5nqB0</recordid><startdate>20090401</startdate><enddate>20090401</enddate><creator>Harvey, Robert</creator><creator>Brown, Kevin</creator><creator>Zhang, Qin</creator><creator>Gartland, Margaret</creator><creator>Walton, Leslie</creator><creator>Talarico, Christine</creator><creator>Lawrence, Wendell</creator><creator>Selleseth, Dean</creator><creator>Coffield, Neil</creator><creator>Leary, Jeffry</creator><creator>Moniri, Kelly</creator><creator>Singer, Sara</creator><creator>Strum, Jay</creator><creator>Gudmundsson, Kristjan</creator><creator>Biron, Karen</creator><creator>Romines, Karen R.</creator><creator>Sethna, Phiroze</creator><general>Elsevier B.V</general><general>Elsevier</general><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>7QO</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20090401</creationdate><title>GSK983: A novel compound with broad-spectrum antiviral activity</title><author>Harvey, Robert ; Brown, Kevin ; Zhang, Qin ; Gartland, Margaret ; Walton, Leslie ; Talarico, Christine ; Lawrence, Wendell ; Selleseth, Dean ; Coffield, Neil ; Leary, Jeffry ; Moniri, Kelly ; Singer, Sara ; Strum, Jay ; Gudmundsson, Kristjan ; Biron, Karen ; Romines, Karen R. ; Sethna, Phiroze</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-b8918733eab85f58539a8b3fc4463c8a5d54fdc3f2fb78327e845cf241c0e1fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenovirus</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Carbazoles - pharmacology</topic><topic>Cell Line, Transformed</topic><topic>Cell Transformation, Viral</topic><topic>Cells, Cultured</topic><topic>DNA Viruses - drug effects</topic><topic>DNA Viruses - physiology</topic><topic>Epstein-Barr virus</topic><topic>GSK983</topic><topic>Herpes simplex virus 1</topic><topic>Human immunodeficiency virus</topic><topic>Human papillomavirus</topic><topic>Human T-lymphotropic virus 1</topic><topic>Humans</topic><topic>Interferon-stimulated genes</topic><topic>Medical sciences</topic><topic>Novel antiviral</topic><topic>Pharmacology. 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50 values of 5–20
nM. Both replication of the adenovirus Ad-5 and the polyoma virus SV-40, and episomal maintenance of human papillomaviruses (HPV) and Epstein-Barr virus (EBV) are susceptible to GSK983. The compound does not inhibit all viruses; herpes simplex virus (HSV-1), human immunodeficiency virus (HIV), and lytic replication of EBV were not susceptible at concentrations below 1
μM. GSK983 does inhibit the growth of cell lines immortalized by HTLV-1, EBV, HPV, SV40 and Ad-5, with EC
50 values in the range of 10–40
nM. Depending on the cell line, the compound induces either apoptosis or cytostasis at concentrations over 20
nM. GSK983 also inhibits cell lines immortalized by non-viral mechanisms, but has little effect on primary cells. The CC
50 values for keratinocytes, fibroblasts, lymphocytes, endothelial, and bone marrow progenitor cells are all above 10
μM. The pattern of inhibition, which includes diverse viruses as well as growth of immortalized cells of varied origins, suggests the target is a host cell protein, rather than a viral protein. Preliminary mechanism studies indicate that GSK983 acts by inducing a subset of interferon-stimulated genes.</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>19187793</pmid><doi>10.1016/j.antiviral.2008.12.015</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0166-3542 |
| ispartof | Antiviral research, 2009-04, Vol.82 (1), p.1-11 |
| issn | 0166-3542 1872-9096 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7114156 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adenovirus Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - pharmacology Apoptosis - drug effects Biological and medical sciences Carbazoles - pharmacology Cell Line, Transformed Cell Transformation, Viral Cells, Cultured DNA Viruses - drug effects DNA Viruses - physiology Epstein-Barr virus GSK983 Herpes simplex virus 1 Human immunodeficiency virus Human papillomavirus Human T-lymphotropic virus 1 Humans Interferon-stimulated genes Medical sciences Novel antiviral Pharmacology. Drug treatments Polyomavirus Simian virus 40 Tetrahydrocarbazole Virus Replication - drug effects |
| title | GSK983: A novel compound with broad-spectrum antiviral activity |
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