{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:08:29Z","timestamp":1790190509309,"version":"4.1.0"},"reference-count":43,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2017,1,25]],"date-time":"2017-01-25T00:00:00Z","timestamp":1485302400000},"content-version":"vor","delay-in-days":366,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["Z01 BC 007333"],"award-info":[{"award-number":["Z01 BC 007333"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["ZIA BC 007363"],"award-info":[{"award-number":["ZIA BC 007363"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>HIV integrase (IN) strand transfer inhibitors (INSTIs) are among the newest anti-AIDS drugs; however, mutant forms of IN can confer resistance. We developed noncytotoxic naphthyridine-containing INSTIs that retain low nanomolar IC50 values against HIV-1 variants harboring all of the major INSTI-resistant mutations. We found by analyzing crystal structures of inhibitors bound to the IN from the prototype foamy virus (PFV) that the most successful inhibitors show striking mimicry of the bound viral DNA prior to 3\u2032-processing and the bound host DNA prior to strand transfer. Using this concept of \u201cbi-substrate mimicry,\u201d we developed a new broadly effective inhibitor that not only mimics aspects of both the bound target and viral DNA but also more completely fills the space they would normally occupy. Maximizing shape complementarity and recapitulating structural components encompassing both of the IN DNA substrates could serve as a guiding principle for the development of new INSTIs.<\/jats:p>","DOI":"10.1021\/acschembio.5b00948","type":"journal-article","created":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T15:09:14Z","timestamp":1453734554000},"page":"1074-1081","source":"Crossref","is-referenced-by-count":41,"title":["HIV-1 Integrase Strand Transfer Inhibitors\nwith Reduced Susceptibility to Drug Resistant Mutant Integrases"],"prefix":"10.1021","volume":"11","author":[{"given":"Xue Zhi","family":"Zhao","sequence":"first","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Frederick, Maryland, United States, 21702"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Smith","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Frederick, Maryland, United States, 21702"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Maskell","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute , , Blanche Lane , , ,","place":["South Mimms, United Kingdom, EN6 3LD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Metifiot","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie E.","family":"Pye","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute , , Blanche Lane , , ,","place":["South Mimms, United Kingdom, EN6 3LD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Fesen","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Marchand","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Pommier","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Cherepanov","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute , , Blanche Lane , , ,","place":["South Mimms, United Kingdom, EN6 3LD"]},{"name":"Imperial College London , St-Mary\u2019s Campus, Norfolk Place , , ,","place":["London, United Kingdom, W2 1PG"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Hughes","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Terrence R.","family":"Burke","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Frederick, Maryland, United States, 21702"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2016,1,25]]},"reference":[{"key":"2026090323082333900_cit1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/nrd3404","article-title":"Interfacial inhibitors:\nTargeting macromolecular complexes","volume":"11","author":"Pommier","year":"2012","journal-title":"Nat. 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Virol."},{"key":"2026090323082333900_cit5","doi-asserted-by":"publisher","first-page":"e1002251","DOI":"10.1371\/journal.pbio.1002251","article-title":"Extremely high mutation rate of HIV-1\nin vivo","volume":"13","author":"Cuevas","year":"2015","journal-title":"PLoS Biol."},{"key":"2026090323082333900_cit6","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1056\/NEJMra1004180","article-title":"Development of antiretroviral\ndrug\nresistance","volume":"365","author":"Wainberg","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"2026090323082333900_cit7","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1128\/AAC.06170-11","article-title":"Broad phenotypic\ncross-resistance\nto elvitegravir in HIV-infected patients failing on raltegravir-containing\nregimens","volume":"56","author":"Garrido","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090323082333900_cit8","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1097\/QCO.0b013e32835a1de7","article-title":"Emerging patterns\nand\nimplications of HIV-1 integrase inhibitor resistance","volume":"25","author":"Geretti","year":"2012","journal-title":"Curr. Opin. Infect. Dis."},{"key":"2026090323082333900_cit9","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1097\/QCO.0b013e32835ba81c","article-title":"Evolution\nof HIV integrase resistance\nmutations","volume":"26","author":"Quashie","year":"2013","journal-title":"Curr. Opin. Infect. 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