BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Identification of a novel type of small molecule inhibitor against HIV-1

  • Kim, Byung Soo (Avixgen Inc.) ;
  • Park, Jung Ae (Avixgen Inc.) ;
  • Kim, Min-Jung (Avixgen Inc.) ;
  • Kim, Seon Hee (National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Yu, Kyung Lee (National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • You, Ji Chang (Avixgen Inc.)
  • 투고 : 2014.11.04
  • 심사 : 2014.11.18
  • 발행 : 2015.02.28
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초록

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 ($IC_{50}$) of $2.0{\mu}M$ in an MT-4 cell-based and cytopathic protection antiviral assay, while its 50% cytotoxic concentration ($CC_{50}$) was much higher than $50{\mu}M$. 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.

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참고문헌

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  1. Anti-HIV Drug Discovery and Development: Current Innovations and Future Trends vol.59, pp.7, 2016, https://doi.org/10.1021/acs.jmedchem.5b00497
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  3. Chloro-1,4-dimethyl-9H-carbazole Derivatives Displaying Anti-HIV Activity vol.23, pp.2, 2018, https://doi.org/10.3390/molecules23020286
  4. Investigation of functional roles of transcription termination factor-1 (TTF-I) in HIV-1 replication vol.51, pp.7, 2018, https://doi.org/10.5483/BMBRep.2018.51.7.032
  5. Investigation of function and regulation of the YB-1 cellular factor in HIV replication vol.51, pp.6, 2018, https://doi.org/10.5483/BMBRep.2018.51.6.231