Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses
The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced i...
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| Veröffentlicht in: | Antiviral research 1994-04, Vol.23 (3), p.203-218 |
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| creator | Lillie, James W. Smee, Donald F. Huffman, John H. Hansen, Lori J. Sidwell, Robert W. Kaddurah-Daouk, Rima |
| description | The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system. |
| doi_str_mv | 10.1016/0166-3542(94)90018-3 |
| format | Article |
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CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/0166-3542(94)90018-3</identifier><identifier>PMID: 8042860</identifier><identifier>CODEN: ARSRDR</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Acyclovir - therapeutic use ; Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agent ; Antiviral agents ; Biological and medical sciences ; Creatine kinase ; Creatinine - analogs & derivatives ; Creatinine - pharmacology ; Creatinine - therapeutic use ; Cyclocreatine ; Disease Models, Animal ; Drug Resistance, Microbial ; Drug Therapy, Combination ; Encephalitis - drug therapy ; Encephalitis - mortality ; Female ; Guanosine Triphosphate - analogs & derivatives ; Guanosine Triphosphate - pharmacology ; Guanosine Triphosphate - therapeutic use ; Herpes Genitalis - microbiology ; Herpes Genitalis - mortality ; Herpes Genitalis - prevention & control ; Herpes virus ; Herpesviridae - drug effects ; Herpesviridae - physiology ; Herpesviridae Infections - drug therapy ; Herpesviridae Infections - mortality ; Human cytomegalovirus ; Humans ; Medical sciences ; Mice ; Microbial Sensitivity Tests ; Pharmacology. Drug treatments ; RNA Viruses - drug effects ; RNA Viruses - physiology ; Survival Rate ; Virus Replication - drug effects</subject><ispartof>Antiviral research, 1994-04, Vol.23 (3), p.203-218</ispartof><rights>1994</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-7158549002fd89c2b3a42efb1a33e3695f5e47a480af90e0ae3ea3426606108e3</citedby><cites>FETCH-LOGICAL-c386t-7158549002fd89c2b3a42efb1a33e3695f5e47a480af90e0ae3ea3426606108e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0166-3542(94)90018-3$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4017604$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8042860$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lillie, James W.</creatorcontrib><creatorcontrib>Smee, Donald F.</creatorcontrib><creatorcontrib>Huffman, John H.</creatorcontrib><creatorcontrib>Hansen, Lori J.</creatorcontrib><creatorcontrib>Sidwell, Robert W.</creatorcontrib><creatorcontrib>Kaddurah-Daouk, Rima</creatorcontrib><title>Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system.</description><subject>Acyclovir - therapeutic use</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agent</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Creatine kinase</subject><subject>Creatinine - analogs & derivatives</subject><subject>Creatinine - pharmacology</subject><subject>Creatinine - therapeutic use</subject><subject>Cyclocreatine</subject><subject>Disease Models, Animal</subject><subject>Drug Resistance, Microbial</subject><subject>Drug Therapy, Combination</subject><subject>Encephalitis - drug therapy</subject><subject>Encephalitis - mortality</subject><subject>Female</subject><subject>Guanosine Triphosphate - analogs & derivatives</subject><subject>Guanosine Triphosphate - pharmacology</subject><subject>Guanosine Triphosphate - therapeutic use</subject><subject>Herpes Genitalis - microbiology</subject><subject>Herpes Genitalis - mortality</subject><subject>Herpes Genitalis - prevention & control</subject><subject>Herpes virus</subject><subject>Herpesviridae - drug effects</subject><subject>Herpesviridae - physiology</subject><subject>Herpesviridae Infections - drug therapy</subject><subject>Herpesviridae Infections - mortality</subject><subject>Human cytomegalovirus</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microbial Sensitivity Tests</subject><subject>Pharmacology. Drug treatments</subject><subject>RNA Viruses - drug effects</subject><subject>RNA Viruses - physiology</subject><subject>Survival Rate</subject><subject>Virus Replication - drug effects</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhi0EKtvCPwApB4Tag8v4I459QUIrCpUqcSlny3EmilESL3ZSsf31eNnVHjl4fJjnHc08hLxjcMuAqU_lKSpqya-NvDEATFPxgmyYbjg1YNRLsjkjr8llzr8AQDVGX5ALDZJrBRuC270fo0_oljBjdc2od6mNf_YTLsN-pJyGKcyxlM49xzF0hbqpwjyENiy5WgasEu7G4Es-zlXsq2Gd3FwNmHaYq6eQ1oz5DXnVuzHj29N_RX7efX3cfqcPP77db788UC-0WmjDal3LcgrvO208b4WTHPuWOSFQKFP3NcrGSQ2uN4DgUKATkisFioFGcUU-HufuUvy9Yl7sFLLHcXQzxjXbRilePPECyiPoU8w5YW93KUwu7S0De7BrD-rsQZ010v6za0WJvT_NX9sJu3PopLP0P5z6Lns39snNPuQzJoE1CmTBPh8xLC6eAiabfcDZYxcS-sV2Mfx_j7-CQZZT</recordid><startdate>19940401</startdate><enddate>19940401</enddate><creator>Lillie, James W.</creator><creator>Smee, Donald F.</creator><creator>Huffman, John H.</creator><creator>Hansen, Lori J.</creator><creator>Sidwell, Robert W.</creator><creator>Kaddurah-Daouk, Rima</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></search><sort><creationdate>19940401</creationdate><title>Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses</title><author>Lillie, James W. ; Smee, Donald F. ; Huffman, John H. ; Hansen, Lori J. ; Sidwell, Robert W. ; Kaddurah-Daouk, Rima</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-7158549002fd89c2b3a42efb1a33e3695f5e47a480af90e0ae3ea3426606108e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Acyclovir - therapeutic use</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agent</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Creatine kinase</topic><topic>Creatinine - analogs & derivatives</topic><topic>Creatinine - pharmacology</topic><topic>Creatinine - therapeutic use</topic><topic>Cyclocreatine</topic><topic>Disease Models, Animal</topic><topic>Drug Resistance, Microbial</topic><topic>Drug Therapy, Combination</topic><topic>Encephalitis - drug therapy</topic><topic>Encephalitis - mortality</topic><topic>Female</topic><topic>Guanosine Triphosphate - analogs & derivatives</topic><topic>Guanosine Triphosphate - pharmacology</topic><topic>Guanosine Triphosphate - therapeutic use</topic><topic>Herpes Genitalis - microbiology</topic><topic>Herpes Genitalis - mortality</topic><topic>Herpes Genitalis - prevention & control</topic><topic>Herpes virus</topic><topic>Herpesviridae - drug effects</topic><topic>Herpesviridae - physiology</topic><topic>Herpesviridae Infections - drug therapy</topic><topic>Herpesviridae Infections - mortality</topic><topic>Human cytomegalovirus</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microbial Sensitivity Tests</topic><topic>Pharmacology. Drug treatments</topic><topic>RNA Viruses - drug effects</topic><topic>RNA Viruses - physiology</topic><topic>Survival Rate</topic><topic>Virus Replication - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lillie, James W.</creatorcontrib><creatorcontrib>Smee, Donald F.</creatorcontrib><creatorcontrib>Huffman, John H.</creatorcontrib><creatorcontrib>Hansen, Lori J.</creatorcontrib><creatorcontrib>Sidwell, Robert W.</creatorcontrib><creatorcontrib>Kaddurah-Daouk, Rima</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><jtitle>Antiviral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lillie, James W.</au><au>Smee, Donald F.</au><au>Huffman, John H.</au><au>Hansen, Lori J.</au><au>Sidwell, Robert W.</au><au>Kaddurah-Daouk, Rima</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses</atitle><jtitle>Antiviral research</jtitle><addtitle>Antiviral Res</addtitle><date>1994-04-01</date><risdate>1994</risdate><volume>23</volume><issue>3</issue><spage>203</spage><epage>218</epage><pages>203-218</pages><issn>0166-3542</issn><eissn>1872-9096</eissn><coden>ARSRDR</coden><abstract>The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>8042860</pmid><doi>10.1016/0166-3542(94)90018-3</doi><tpages>16</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Antiviral research, 1994-04, Vol.23 (3), p.203-218 |
| issn | 0166-3542 1872-9096 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Acyclovir - therapeutic use Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agent Antiviral agents Biological and medical sciences Creatine kinase Creatinine - analogs & derivatives Creatinine - pharmacology Creatinine - therapeutic use Cyclocreatine Disease Models, Animal Drug Resistance, Microbial Drug Therapy, Combination Encephalitis - drug therapy Encephalitis - mortality Female Guanosine Triphosphate - analogs & derivatives Guanosine Triphosphate - pharmacology Guanosine Triphosphate - therapeutic use Herpes Genitalis - microbiology Herpes Genitalis - mortality Herpes Genitalis - prevention & control Herpes virus Herpesviridae - drug effects Herpesviridae - physiology Herpesviridae Infections - drug therapy Herpesviridae Infections - mortality Human cytomegalovirus Humans Medical sciences Mice Microbial Sensitivity Tests Pharmacology. Drug treatments RNA Viruses - drug effects RNA Viruses - physiology Survival Rate Virus Replication - drug effects |
| title | Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses |
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