{"corpus_id":8613755,"paper_sha":"663177e530cce09ec92152e2e251540cf92b6762","doi":"10.1073/PNAS.74.12.5716","arxiv_id":null,"pmid":202961,"pmcid":"PMC431864","mag_id":2045360603,"dblp_id":null,"acl_id":null,"title":"Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine.","year":1977,"publication_date":"1977-12-01","venue":"Proceedings of the National Academy of Sciences of the United States of America","journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","pages":"\n          5716-20\n        ","volume":"74 12"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine","Chemistry"],"reference_count":1,"citation_count":1487,"influential_citation_count":26,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Antiviral Agents","mj":true,"ui":"D000998"},{"d":"Cell Line","mj":false,"ui":"D002460"},{"d":"DNA-Directed DNA Polymerase","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D004259"},{"d":"Guanine","mj":false,"qs":[{"q":"analogs & derivatives","mj":true,"ui":"Q000031"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D006147"},{"d":"Guanine Nucleotides","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D006150"},{"d":"Kinetics","mj":false,"ui":"D007700"},{"d":"Phosphotransferases","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D010770"},{"d":"Simplexvirus","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"},{"q":"enzymology","mj":false,"ui":"Q000201"}],"ui":"D018139"},{"d":"Thymidine Kinase","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D013937"}],"chemicals":[{"n":"Antiviral Agents","ui":"D000998","reg":"0"},{"n":"Guanine Nucleotides","ui":"D006150","reg":"0"},{"n":"Guanine","ui":"D006147","reg":"5Z93L87A1R"},{"n":"Phosphotransferases","ui":"D010770","reg":"EC 2.7.-"},{"n":"Thymidine Kinase","ui":"D013937","reg":"EC 2.7.1.21"},{"n":"DNA-Directed DNA Polymerase","ui":"D004259","reg":"EC 2.7.7.7"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"A guanine derivative with an acyclic side chain, 2-hydroxyethoxymethyl, at position 9 has potent antiviral activity [dose for 50% inhibition (ED(50)) = 0.1 muM] against herpes simplex virus type 1. This acyclic nucleoside analog, termed acycloguanosine, is converted to a monophosphate by a virus-specified pyrimidine deoxynucleoside (thymidine) kinase and is subsequently converted to acycloguanosine di- and triphosphates. In the uninfected host cell (Vero) these phosphorylations of acycloguanosine occur to a very limited extent. Acycloguanosine triphosphate inhibits herpes simplex virus DNA polymerase (DNA nucleotidyltransferase) 10-30 times more effectively than cellular (HeLa S3) DNA polymerase. These factors contribute to the drug's selectivity; inhibition of growth of the host cell requires a 3000-fold greater concentration of drug than does the inhibition of viral multiplication. There is, moreover, the strong possibility of chain termination of the viral DNA by incorporation of acycloguanosine. The identity of the kinase that phosphorylates acycloguanosine was determined after separation of the cellular and virus-specified thymidine kinase activities by affinity chromatography, by reversal studies with thymidine, and by the lack of monophosphate formation in a temperature-sensitive, thymidine kinase-deficient mutant of the KOS strain of herpes simplex virus type 1 (tsA1).","claims":[{"public_id":"cl_76db06a1baf6a4c999df90e27780da84","status":"active","text":"Acycloguanosine is converted to its monophosphate by a virus-specified thymidine kinase and then further phosphorylated to di- and triphosphate forms, whereas these phosphorylations occur to only a very limited extent in uninfected Vero cells.","confidence":0.9,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_76db06a1baf6a4c999df90e27780da84"},{"public_id":"cl_f42a64cc5c4116c6dfe7badc5810011e","status":"active","text":"Acycloguanosine shows potent antiviral activity against herpes simplex virus type 1, with a 50% inhibitory dose (ED50) of 0.1 µM.","confidence":0.95,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_f42a64cc5c4116c6dfe7badc5810011e"},{"public_id":"cl_3871ea4d7824766c70cf1db0f7516117","status":"active","text":"Acycloguanosine triphosphate inhibits herpes simplex virus DNA polymerase 10 to 30 times more effectively than it inhibits HeLa S3 cellular DNA polymerase.","confidence":0.9,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_3871ea4d7824766c70cf1db0f7516117"},{"public_id":"cl_3b7acd2dd0ec3418126a0da9d7461618","status":"active","text":"Inhibition of host cell growth requires roughly 3000-fold greater acycloguanosine concentration than inhibition of viral multiplication, reflecting the drug's selectivity for infected cells.","confidence":0.85,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_3b7acd2dd0ec3418126a0da9d7461618"},{"public_id":"cl_965fba28437f4f9dcf44b2181c08978a","status":"active","text":"The virus-specified thymidine kinase is identified as the enzyme phosphorylating acycloguanosine, based on affinity chromatography separation of cellular and viral kinase activities, thymidine reversal experiments, and the absence of monophosphate formation in the thymidine kinase-deficient mutant (tsA1) of the KOS strain of herpes simplex virus type 1.","confidence":0.85,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_965fba28437f4f9dcf44b2181c08978a"}],"concepts":[{"public_id":"co_109fa94189fdb279ec742bb1fd2f85c0","status":"active","name":"acycloguanosine triphosphate","description":"The fully phosphorylated, active metabolite of acycloguanosine formed after virus-specified kinase activity.","types":["metabolite"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_109fa94189fdb279ec742bb1fd2f85c0"},{"public_id":"co_39a5ccd6d6ab78e3a385077b3af46398","status":"active","name":"thymidine kinase-deficient mutant (tsA1)","description":"A temperature-sensitive, thymidine kinase-deficient mutant of the KOS strain of herpes simplex virus type 1 used to test acycloguanosine phosphorylation.","types":["viral mutant strain"],"aliases":["tsA1"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_39a5ccd6d6ab78e3a385077b3af46398"},{"public_id":"co_501a4933d2cfd396de57f2f503241ae0","status":"active","name":"KOS strain","description":"The herpes simplex virus type 1 strain background from which the tsA1 thymidine kinase-deficient mutant was derived.","types":["viral strain"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_501a4933d2cfd396de57f2f503241ae0"},{"public_id":"co_5c69df5a95acb26bb4146f5b39bb765d","status":"active","name":"50% inhibitory dose (ED50)","description":"The drug concentration measure used to quantify antiviral potency of acycloguanosine against herpes simplex virus type 1.","types":["measure"],"aliases":["ED50","dose for 50% inhibition"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_5c69df5a95acb26bb4146f5b39bb765d"},{"public_id":"co_67fb9a007f00e32eb805d3f3cd6ece47","status":"active","name":"herpes simplex virus DNA polymerase","description":"The viral DNA-synthesizing enzyme targeted for inhibition by acycloguanosine triphosphate.","types":["enzyme"],"aliases":["DNA nucleotidyltransferase"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_67fb9a007f00e32eb805d3f3cd6ece47"},{"public_id":"co_864d34fcd70ded15b60a547453916e7b","status":"active","name":"HeLa S3 cellular DNA polymerase","description":"The host cell (HeLa S3) DNA polymerase used as a comparator enzyme for assessing viral selectivity of acycloguanosine triphosphate.","types":["enzyme"],"aliases":["cellular DNA polymerase"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_864d34fcd70ded15b60a547453916e7b"},{"public_id":"co_9506841404516c51d45819f16a5275fe","status":"active","name":"virus-specified thymidine kinase","description":"A herpes simplex virus-encoded kinase that phosphorylates acycloguanosine to its monophosphate form.","types":["enzyme"],"aliases":["pyrimidine deoxynucleoside kinase"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_9506841404516c51d45819f16a5275fe"},{"public_id":"co_bca0e11addb926c3946376dd40dd3d15","status":"active","name":"herpes simplex virus type 1","description":"The virus species against which acycloguanosine's antiviral activity and selectivity are evaluated in this study.","types":["virus"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_bca0e11addb926c3946376dd40dd3d15"},{"public_id":"co_bdb943601ceab68df260255ac52cdbc9","status":"active","name":"affinity chromatography","description":"A separation method used here to distinguish cellular and virus-specified thymidine kinase activities.","types":["method"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_bdb943601ceab68df260255ac52cdbc9"},{"public_id":"co_cb28bdd75027e5bb3043950fcd37223e","status":"active","name":"Vero cells","description":"An uninfected host cell line used to assess background phosphorylation of acycloguanosine and drug toxicity.","types":["cell line"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_cb28bdd75027e5bb3043950fcd37223e"},{"public_id":"co_f56e2143c41c5aeb2119a41f333a724d","status":"active","name":"chain termination","description":"A proposed mechanism by which incorporation of acycloguanosine into viral DNA halts further DNA chain extension.","types":["mechanism"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_f56e2143c41c5aeb2119a41f333a724d"},{"public_id":"co_f868ea988d086075826e66302e244c77","status":"active","name":"acycloguanosine","description":"An acyclic guanine nucleoside analog with a 2-hydroxyethoxymethyl side chain at the 9 position, studied here as an antiherpetic agent.","types":["drug","nucleoside analog"],"aliases":["9-(2-hydroxyethoxymethyl) guanine"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_f868ea988d086075826e66302e244c77"}],"external_ids":{"DOI":"10.1073/PNAS.74.12.5716","ArXiv":null,"PubMed":202961,"PubMedCentral":"PMC431864","MAG":2045360603,"DBLP":null,"ACL":null},"open_access":{"is_open_access":false,"pdf_url":null,"landing_url":"https://sah.borca.ai/papers/8613755","source":null,"pdf_url_source":null,"license":null,"reason":"pdf_url_not_indexed"},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":631814,"paper_uid":"eac70c1f-efd9-4e1c-a330-c94b96eb0fb4","canonical_identity":{"paper_id":631814,"paper_uid":"eac70c1f-efd9-4e1c-a330-c94b96eb0fb4","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/8613755"}