title: Mechanism of inhibitory effect of NCC164 on replication of human immunodeficiency virus.
abstract: The effect of a novel anti-HIV (human immunodeficiency virus) compound, designated NCC164, has been studied with HIV infected cultures. The agent exhibited concentration-dependent inhibition of HIV replication in primary infected cultures of H9 cell line and PBMCs. Substantial inhibition of viral replication was observed at concentration of NCC164 that showed little cytotoxicity. The ratio of IC50 values for the MTT (3-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide) to RT (reverse transcriptase) assays means the selectivity index was more than 100. In attempting to define the inhibitory mechanism of NCC164, we investigated its effect on each step of HIV replication. This agent was highly effective against HIV replication regardless of the addition period during early stages of infection (adsorption to integration) but did not inhibit reverse transcriptase activity directly. The agent efficiently blocked virus maturation without side effect and the number of progeny produced by NCC164-treated cells was markedly reduced.
authors.affiliation: Department of Microbiology, Jikei University School of Medicine, Tokyo, Japan. nakamura@jikei.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Terada
authors.forename: K
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Ohno
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015394:Molecular Structure; D012367:RNA, Viral; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D020298:U937 Cells; D014779:Virus Replication / Q000187:drug effects*; D014966:Xanthenes / Q000494:pharmacology*
chemical_list: C434924:2'-O-tetrahydropyranyl-3',5'-O-di(9-phenylxanthenyl)adenosine; D019380:Anti-HIV Agents; D012367:RNA, Viral; D014966:Xanthenes; D054303:HIV Reverse Transcriptase; D000241:Adenosine