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This bistriazoloacridone derivative exerted its mechanism of antiviral action through selective inhibition of HIV-1 transcription during the postintegrative phase of virus replication. Mechanistic studies revealed that temacrazine blocked HIV-1 RNA formation without interference with the transcription of cellular genes or with events associated with the HIV-1 Tat and Rev regulatory proteins. Although temacrazine inhibited the in vitro 3\u2032 processing and strand transfer activities of HIV-1 integrase, with a 50% inhibitory concentration of approximately 50 nM, no evidence of an inhibitory effect on the intracellular integration of proviral DNA into the cellular genome during the early phase of infection could be detected. Furthermore, temacrazine did not interfere with virus attachment or fusion to host cells or the enzymatic activities of HIV-1 reverse transcriptase or protease, and the compound was not directly virucidal. Demonstration of in vivo anti-HIV-1 activity by temacrazine identifies bistriazoloacridones as a new class of pharmaceuticals that selectively blocks HIV-1 transcription.<\/jats:p>","DOI":"10.1128\/aac.42.3.487","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:30:35Z","timestamp":1539045035000},"page":"487-494","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Inhibition of Acute-, Latent-, and Chronic-Phase Human Immunodeficiency Virus Type 1 (HIV-1) Replication by a Bistriazoloacridone Analog That Selectively Inhibits HIV-1 Transcription"],"prefix":"10.1128","volume":"42","author":[{"given":"Jim A.","family":"Turpin","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Laboratory of Antiviral Drug Mechanisms, Developmental Therapeutics Program, SAIC Frederick,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Robert W.","family":"Buckheit","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Virology Research Group, Southern Research Institute-Frederick Research Center, Frederick, Maryland 217012"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Derse","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Laboratory of Leukocyte Biology, Division of Basic Sciences,3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda","family":"Hollingshead","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Biological Testing Branch, Developmental Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers,4 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Williamson","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Laboratory of Antiviral Drug Mechanisms, Developmental Therapeutics Program, SAIC Frederick,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Palamone","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Laboratory of Antiviral Drug Mechanisms, Developmental Therapeutics Program, SAIC Frederick,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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