title: Identification and characterization of a new type of inhibitor against the human immunodeficiency virus type-1 nucleocapsid protein.
abstract: BACKGROUND
  The human immunodeficiency virus type-1 (HIV-1) nucleocapsid protein (NC) is an essential and multifunctional protein involved in multiple stages of the viral life cycle such as reverse transcription, integration of proviral DNA, and especially genome RNA packaging. For this reason, it has been considered as an attractive target for the development of new anti-HIV drugs. Although a number of inhibitors of NC have been reported thus far, the search for NC-specific and functional inhibitor(s) with a good antiviral activity continues.
  
  
  RESULTS
  In this study, we report the identification of A1752, a small molecule with inhibitory action against HIV-1 NC, which shows a strong antiviral efficacy and an IC50 around 1 μM. A1752 binds directly to HIV-1 NC, thereby inhibiting specific chaperone functions of NC including Psi RNA dimerization and complementary trans-activation response element (cTAR) DNA destabilization, and it also disrupts the proper Gag processing. Further analysis of the mechanisms of action of A1752 also showed that it generates noninfectious viral particles with defects in uncoating and reverse transcription in the infected cells.
  
  
  CONCLUSIONS
  These results demonstrate that A1752 is a specific and functional inhibitor of NC with a novel mode of action and good antiviral efficacy. Thus, this agent provides a new type of anti-HIV NC inhibitor candidate for further drug development.
authors.affiliation: Avixgen Inc., Seoul, 137-701, Korea. mjkim208@avixgen.com.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Avixgen Inc., Seoul, 137-701, Korea. danielle1011@naver.com.|National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea. danielle1011@naver.com.
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Avixgen Inc., Seoul, 137-701, Korea. love11901@naver.com.
authors.forename: Jung Ae
authors.initials: JA
authors.lastname: Park
authors.affiliation: National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea. smashing20@hanmail.net.
authors.forename: Kyung Lee
authors.initials: KL
authors.lastname: Yu
authors.affiliation: National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea. sooin0430@hotmail.com.
authors.forename: Soo In
authors.initials: SI
authors.lastname: Jang
authors.affiliation: Avixgen Inc., Seoul, 137-701, Korea. 9-jiwon@hanmail.net.
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea. fighteunyou@hanmail.net.
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Avixgen Inc., Seoul, 137-701, Korea. jiyou@catholic.ac.kr.|National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea. jiyou@catholic.ac.kr.
authors.forename: Ji Chang
authors.initials: JC
authors.lastname: You
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019281:Dimerization; D055808:Drug Discovery; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D019590:Nucleocapsid Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011422:Propionates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D053778:Thiazolidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C000609120:A1752 compound; D019380:Anti-HIV Agents; D018832:Molecular Chaperones; D019590:Nucleocapsid Proteins; D011422:Propionates; D012367:RNA, Viral; D053778:Thiazolidines; D054301:gag Gene Products, Human Immunodeficiency Virus