Baseline sensitivity of HSV-1 and HSV-2 clinical isolates and defined acyclovir-resistant strains to the helicase–primase inhibitor pritelivir
•USA HSV clinical isolates are sensitive to helicase–primase inhibitor, pritelivir.•HSV-2 strains show more individual variation than HSV-1 strains.•HSV-1 strains with acyclovir resistance mutations are sensitive to pritelivir.•These data provide baseline data pre-wide exposure to helicase–primase i...
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| Veröffentlicht in: | Antiviral research 2013-11, Vol.100 (2), p.297-299 |
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| creator | Field, Hugh J. Huang, Meei-Li Lay, Elizabeth M. Mickleburgh, Ian Zimmermann, Holger Birkmann, Alexander |
| description | •USA HSV clinical isolates are sensitive to helicase–primase inhibitor, pritelivir.•HSV-2 strains show more individual variation than HSV-1 strains.•HSV-1 strains with acyclovir resistance mutations are sensitive to pritelivir.•These data provide baseline data pre-wide exposure to helicase–primase inhibitors.
Fifty-nine US isolates of HSV-1 and HSV-2 obtained between 1998 and 2004 were tested for sensitivity to the helicase–primase inhibitor, pritelivir (AIC316, BAY 57-1293) by plaque-reduction assay. All isolates, which were collected prior to any clinical use of primase–helicase inhibitors, were sensitive and showed mean EC50 values of 0.026 and 0.029μM for HSV-1 and HSV-2, respectively. Furthermore, several laboratory-selected acyclovir-resistant HSV mutants were also sensitive to pritelivir. These data provide a baseline for HSV sensitivity to pritelivir in general population before it is introduced and broadly used to treat HSV infection. The data also validate pritelivir as an appropriate therapy for nucleoside-resistant HSV infections. |
| doi_str_mv | 10.1016/j.antiviral.2013.08.024 |
| format | Article |
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Fifty-nine US isolates of HSV-1 and HSV-2 obtained between 1998 and 2004 were tested for sensitivity to the helicase–primase inhibitor, pritelivir (AIC316, BAY 57-1293) by plaque-reduction assay. All isolates, which were collected prior to any clinical use of primase–helicase inhibitors, were sensitive and showed mean EC50 values of 0.026 and 0.029μM for HSV-1 and HSV-2, respectively. Furthermore, several laboratory-selected acyclovir-resistant HSV mutants were also sensitive to pritelivir. These data provide a baseline for HSV sensitivity to pritelivir in general population before it is introduced and broadly used to treat HSV infection. The data also validate pritelivir as an appropriate therapy for nucleoside-resistant HSV infections.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2013.08.024</identifier><identifier>PMID: 24021190</identifier><identifier>CODEN: ARSRDR</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>Acyclovir - pharmacology ; AIC316 ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Antiviral Agents - pharmacology ; BAY 57-1293 ; Biological and medical sciences ; DNA Helicases - antagonists & inhibitors ; Helicase–primase ; Herpes simplex virus 1 ; Herpesvirus 1, Human - drug effects ; Herpesvirus 1, Human - isolation & purification ; Herpesvirus 2, Human - drug effects ; Herpesvirus 2, Human - isolation & purification ; HSV ; Humans ; Medical sciences ; Microbial Sensitivity Tests ; Pharmacology. Drug treatments ; Pritelivir ; Pyridines - pharmacology ; Thiazoles - pharmacology ; United States ; Viral Plaque Assay</subject><ispartof>Antiviral research, 2013-11, Vol.100 (2), p.297-299</ispartof><rights>2013 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2013 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-6a02b1a49217221d7c44de9df56233d83edc3bffa8dabef917386498613110513</citedby><cites>FETCH-LOGICAL-c434t-6a02b1a49217221d7c44de9df56233d83edc3bffa8dabef917386498613110513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.antiviral.2013.08.024$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3538,27906,27907,45977</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27952988$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24021190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Field, Hugh J.</creatorcontrib><creatorcontrib>Huang, Meei-Li</creatorcontrib><creatorcontrib>Lay, Elizabeth M.</creatorcontrib><creatorcontrib>Mickleburgh, Ian</creatorcontrib><creatorcontrib>Zimmermann, Holger</creatorcontrib><creatorcontrib>Birkmann, Alexander</creatorcontrib><title>Baseline sensitivity of HSV-1 and HSV-2 clinical isolates and defined acyclovir-resistant strains to the helicase–primase inhibitor pritelivir</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>•USA HSV clinical isolates are sensitive to helicase–primase inhibitor, pritelivir.•HSV-2 strains show more individual variation than HSV-1 strains.•HSV-1 strains with acyclovir resistance mutations are sensitive to pritelivir.•These data provide baseline data pre-wide exposure to helicase–primase inhibitors.
Fifty-nine US isolates of HSV-1 and HSV-2 obtained between 1998 and 2004 were tested for sensitivity to the helicase–primase inhibitor, pritelivir (AIC316, BAY 57-1293) by plaque-reduction assay. All isolates, which were collected prior to any clinical use of primase–helicase inhibitors, were sensitive and showed mean EC50 values of 0.026 and 0.029μM for HSV-1 and HSV-2, respectively. Furthermore, several laboratory-selected acyclovir-resistant HSV mutants were also sensitive to pritelivir. These data provide a baseline for HSV sensitivity to pritelivir in general population before it is introduced and broadly used to treat HSV infection. The data also validate pritelivir as an appropriate therapy for nucleoside-resistant HSV infections.</description><subject>Acyclovir - pharmacology</subject><subject>AIC316</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>BAY 57-1293</subject><subject>Biological and medical sciences</subject><subject>DNA Helicases - antagonists & inhibitors</subject><subject>Helicase–primase</subject><subject>Herpes simplex virus 1</subject><subject>Herpesvirus 1, Human - drug effects</subject><subject>Herpesvirus 1, Human - isolation & purification</subject><subject>Herpesvirus 2, Human - drug effects</subject><subject>Herpesvirus 2, Human - isolation & purification</subject><subject>HSV</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Pharmacology. Drug treatments</subject><subject>Pritelivir</subject><subject>Pyridines - pharmacology</subject><subject>Thiazoles - pharmacology</subject><subject>United States</subject><subject>Viral Plaque Assay</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctuFDEQRS0EIkPgF8AbJDbd-NVuexkiIEiRWPDYWh67WuNRT3ewPZFmxycg5Q_zJdQ8CMusXHKdqnvtS8gbzlrOuH6_bv1U023KfmwF47JlpmVCPSELbnrRWGb1U7JAUjeyU-KMvChlzRjTvTXPyZlQTHBu2YL8-eALjGkCWmAqab-z7ug80KtvPxtO_RQPlaABoRT8SFOZR1-hHHoRBpyN1IddGGf002QoqVR0R0vNPk2F1pnWFdAVygQUu_99d5PTBiuaplVapjpnijcV-7jgJXk2-LHAq9N5Tn58-vj98qq5_vr5y-XFdROUVLXRnokl98oK3gvBYx-UimDj0GkhZTQSYpDLYfAm-iUMlvfSaGWN5pJz1nF5Tt4d997k-dcWSnWbVAKMo59g3hbHda9lJ1RnH0cV2uhtJztE-yMa8lxKhsEd3pp3jjO3T86t3UNybp-cY8Zhcjj5-iSyXW4gPsz9iwqBtyfAF8xhyH4Kqfzn0ICwxiB3ceQAf-82QXYlJJgCxJQhVBfn9KiZv-k3ve4</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Field, Hugh J.</creator><creator>Huang, Meei-Li</creator><creator>Lay, Elizabeth M.</creator><creator>Mickleburgh, Ian</creator><creator>Zimmermann, Holger</creator><creator>Birkmann, Alexander</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>7X8</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>20131101</creationdate><title>Baseline sensitivity of HSV-1 and HSV-2 clinical isolates and defined acyclovir-resistant strains to the helicase–primase inhibitor pritelivir</title><author>Field, Hugh J. ; Huang, Meei-Li ; Lay, Elizabeth M. ; Mickleburgh, Ian ; Zimmermann, Holger ; Birkmann, Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-6a02b1a49217221d7c44de9df56233d83edc3bffa8dabef917386498613110513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acyclovir - pharmacology</topic><topic>AIC316</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>BAY 57-1293</topic><topic>Biological and medical sciences</topic><topic>DNA Helicases - antagonists & inhibitors</topic><topic>Helicase–primase</topic><topic>Herpes simplex virus 1</topic><topic>Herpesvirus 1, Human - drug effects</topic><topic>Herpesvirus 1, Human - isolation & purification</topic><topic>Herpesvirus 2, Human - drug effects</topic><topic>Herpesvirus 2, Human - isolation & purification</topic><topic>HSV</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>Pharmacology. Drug treatments</topic><topic>Pritelivir</topic><topic>Pyridines - pharmacology</topic><topic>Thiazoles - pharmacology</topic><topic>United States</topic><topic>Viral Plaque Assay</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Field, Hugh J.</creatorcontrib><creatorcontrib>Huang, Meei-Li</creatorcontrib><creatorcontrib>Lay, Elizabeth M.</creatorcontrib><creatorcontrib>Mickleburgh, Ian</creatorcontrib><creatorcontrib>Zimmermann, Holger</creatorcontrib><creatorcontrib>Birkmann, Alexander</creatorcontrib><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>MEDLINE - Academic</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><jtitle>Antiviral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Field, Hugh J.</au><au>Huang, Meei-Li</au><au>Lay, Elizabeth M.</au><au>Mickleburgh, Ian</au><au>Zimmermann, Holger</au><au>Birkmann, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Baseline sensitivity of HSV-1 and HSV-2 clinical isolates and defined acyclovir-resistant strains to the helicase–primase inhibitor pritelivir</atitle><jtitle>Antiviral research</jtitle><addtitle>Antiviral Res</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>100</volume><issue>2</issue><spage>297</spage><epage>299</epage><pages>297-299</pages><issn>0166-3542</issn><eissn>1872-9096</eissn><coden>ARSRDR</coden><abstract>•USA HSV clinical isolates are sensitive to helicase–primase inhibitor, pritelivir.•HSV-2 strains show more individual variation than HSV-1 strains.•HSV-1 strains with acyclovir resistance mutations are sensitive to pritelivir.•These data provide baseline data pre-wide exposure to helicase–primase inhibitors.
Fifty-nine US isolates of HSV-1 and HSV-2 obtained between 1998 and 2004 were tested for sensitivity to the helicase–primase inhibitor, pritelivir (AIC316, BAY 57-1293) by plaque-reduction assay. All isolates, which were collected prior to any clinical use of primase–helicase inhibitors, were sensitive and showed mean EC50 values of 0.026 and 0.029μM for HSV-1 and HSV-2, respectively. Furthermore, several laboratory-selected acyclovir-resistant HSV mutants were also sensitive to pritelivir. These data provide a baseline for HSV sensitivity to pritelivir in general population before it is introduced and broadly used to treat HSV infection. The data also validate pritelivir as an appropriate therapy for nucleoside-resistant HSV infections.</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>24021190</pmid><doi>10.1016/j.antiviral.2013.08.024</doi><tpages>3</tpages></addata></record> |
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| subjects | Acyclovir - pharmacology AIC316 Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - pharmacology BAY 57-1293 Biological and medical sciences DNA Helicases - antagonists & inhibitors Helicase–primase Herpes simplex virus 1 Herpesvirus 1, Human - drug effects Herpesvirus 1, Human - isolation & purification Herpesvirus 2, Human - drug effects Herpesvirus 2, Human - isolation & purification HSV Humans Medical sciences Microbial Sensitivity Tests Pharmacology. Drug treatments Pritelivir Pyridines - pharmacology Thiazoles - pharmacology United States Viral Plaque Assay |
| title | Baseline sensitivity of HSV-1 and HSV-2 clinical isolates and defined acyclovir-resistant strains to the helicase–primase inhibitor pritelivir |
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