Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

Antimicrob Agents Chemother. 2016 Sep 23;60(10):5731-41. doi: 10.1128/AAC.00341-16. Print 2016 Oct.


Three compounds (1, 2, and 3) previously reported to inhibit HIV-1 replication and/or in vitro activity of reverse transcriptase were studied, but only fullerene derivatives 1 and 2 showed strong antiviral activity on the replication of HIV-1 in human CD4(+) T cells. However, these compounds did not inhibit infection by single-round infection vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped viruses, indicating no effect on the early steps of the viral life cycle. In contrast, analysis of single-round infection VSV-G-pseudotyped HIV-1 produced in the presence of compound 1 or 2 showed a complete lack of infectivity in human CD4(+) T cells, suggesting that the late stages of the HIV-1 life cycle were affected. Quantification of virion-associated viral RNA and p24 indicates that RNA packaging and viral production were unremarkable in these viruses. However, Gag and Gag-Pol processing was affected, as evidenced by immunoblot analysis with an anti-p24 antibody and the measurement of virion-associated reverse transcriptase activity, ratifying the effect of the fullerene derivatives on virion maturation of the HIV-1 life cycle. Surprisingly, fullerenes 1 and 2 did not inhibit HIV-1 protease in an in vitro assay at the doses that potently blocked viral infectivity, suggesting a protease-independent mechanism of action. Highlighting the potential therapeutic relevance of fullerene derivatives, these compounds block infection by HIV-1 resistant to protease and maturation inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / virology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Drug Resistance, Viral / drug effects
  • Fullerenes / chemistry
  • Fullerenes / pharmacology*
  • HIV Core Protein p24 / metabolism
  • HIV Protease Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • HIV-1 / pathogenicity
  • HIV-1 / physiology
  • Humans
  • Virion / drug effects
  • Virus Replication / drug effects
  • gag Gene Products, Human Immunodeficiency Virus / metabolism


  • Anti-HIV Agents
  • Fullerenes
  • HIV Core Protein p24
  • HIV Protease Inhibitors
  • gag Gene Products, Human Immunodeficiency Virus
  • p24 protein, Human Immunodeficiency Virus Type 1