The Bis-Azo Compound FP-21399 Inhibits HIV-1 Replication by Preventing Viral Entry

Virology. 1998 May 10;244(2):530-41. doi: 10.1006/viro.1998.9115.

Abstract

The bis-azo compound FP-21399 inhibits HIV-1 infection. We now show that FP-21399 acts on the HIV-1 envelope glycoprotein to prevent viral replication. This compound targets the entry step of the HIV-1 replication cycle as demonstrated by time-of-addition and single cycle viral entry assays. The entry of SIVmac239, which uses the same coreceptors (CD4/CCR5) as HIV-1, was not inhibited by FP-21399, indicating that the antiviral effect of FP-21399 is specific for the HIV-1 envelope glycoprotein and is not dependent upon the cellular receptors CD4 and CCR5. FP-21399 inhibits neither the activity of HIV-1 reverse transcriptase nor the expression of HIV-1 early mRNA. Finally, this compound inhibits gp120 shedding of the T-tropic virus. Our results suggest that the anti-HIV activity of FP-21399 is due to its interaction with HIV-1 gp120/41 complex during viral entry.

Publication types

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

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology*
  • Base Sequence
  • Chlorobenzenes / pharmacology*
  • DNA Primers / genetics
  • Gene Expression / drug effects
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp41 / metabolism
  • HIV Infections / prevention & control
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • In Vitro Techniques
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / virology
  • Membrane Fusion / drug effects
  • Naphthalenes / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Receptors, CCR5 / drug effects
  • Receptors, CCR5 / physiology
  • Receptors, CXCR4 / drug effects
  • Receptors, CXCR4 / physiology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / pathogenicity
  • Virus Replication / drug effects*

Substances

  • Anti-HIV Agents
  • Chlorobenzenes
  • DNA Primers
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Naphthalenes
  • RNA, Messenger
  • RNA, Viral
  • Receptors, CCR5
  • Receptors, CXCR4
  • FP 21399