title: Identification of a novel type of small molecule inhibitor against HIV-1.
abstract: Here we report a new chemical inhibitor against HIV-1 with a novel structure and mode of action. The inhibitor, designated as A1836, inhibited HIV-1 replication and virus production with a 50% inhibitory concentration (IC₅₀) of 2.0 μM in an MT-4 cell-based and cytopathic protection antiviral assay, while its 50% cytotoxic concentration (CC₅₀) was much higher than 50 μM. Examination of the effect of A1836 on in vitro HIV-1 reverse transcriptase (RT) and integrase showed that neither were molecular targets of A1836. The characterization and re-infection assay of the HIV-1 virions generated in the presence of A1836 showed that the synthesis of early RT products in the cells infected with the virions was inhibited dose-dependently, due in part to abnormal protein formation within the virions, thus resulting in an impaired infectivity. These results suggest that A1836 might be a novel candidate for the development of a new type of HIV-1 inhibitor.
authors.affiliation: Avixgen Inc. Seoul 137-701, Korea.
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Avixgen Inc. Seoul 137-701, Korea.
authors.forename: Jung Ae
authors.initials: JA
authors.lastname: Park
authors.affiliation: Avixgen Inc. Seoul 137-701, Korea.
authors.forename: Min-Jung
authors.initials: MJ
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.
authors.forename: Seon Hee
authors.initials: SH
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.
authors.forename: Kyung Lee
authors.initials: KL
authors.lastname: Yu
authors.affiliation: Avixgen Inc.; National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Ji Chang
authors.initials: JC
authors.lastname: You
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D019427:HIV Integrase / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010957:Plasmids / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C000602850:(1-(4-chlorobenzyl)-N-(2-methoxybenzyl)-1H-pyrazole-3-carboxamide; D000998:Antiviral Agents; D011720:Pyrazoles; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019427:HIV Integrase; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase