title: The bis-azo compound FP-21399 inhibits HIV-1 replication by preventing viral entry.
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.
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Choe
authors.forename: B J
authors.initials: BJ
authors.lastname: Dezube
authors.forename: M
authors.initials: M
authors.lastname: Farzan
authors.forename: P L
authors.initials: PL
authors.lastname: Sharma
authors.forename: X C
authors.initials: XC
authors.lastname: Zhou
authors.forename: L B
authors.initials: LB
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: S
authors.initials: S
authors.lastname: Gillies
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: J G
authors.initials: JG
authors.lastname: Sodroski
authors.forename: C S
authors.initials: CS
authors.lastname: Crumpacker
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D002722:Chlorobenzenes / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008561:Membrane Fusion / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000187:drug effects / Q000502:physiology; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000502:physiology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000472:pathogenicity; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D002722:Chlorobenzenes; D017931:DNA Primers; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D009281:Naphthalenes; D012333:RNA, Messenger; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C106790:FP 21399