lomofungin and 2-2--((3-3--dimethoxy(1-1--biphenyl)-4-4--diyl)diimino)bis-benzoic-acid

lomofungin has been researched along with 2-2--((3-3--dimethoxy(1-1--biphenyl)-4-4--diyl)diimino)bis-benzoic-acid* in 1 studies

Other Studies

1 other study(ies) available for lomofungin and 2-2--((3-3--dimethoxy(1-1--biphenyl)-4-4--diyl)diimino)bis-benzoic-acid

Article	Year
Redoxal, an inhibitor of de novo pyrimidine biosynthesis, augments APOBEC3G antiviral activity against human immunodeficiency virus type 1. Virology, 2015, Volume: 484 APOBEC3G (A3G) is a cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA; deamination-independent mechanisms are also implicated. HIV-1 Vif protein counteracts A3G by inducing its proteasomal degradation. Thus, the Vif-A3G axis is a potential therapeutic target. To identify compounds that inhibit Vif:A3G interaction, a 307,520 compound library was tested in a TR-FRET screen. Two identified compounds, redoxal and lomofungin, inhibited HIV-1 replication in peripheral blood mononuclear cells. Lomofungin activity was linked to A3G, but not pursued further due to cytotoxicity. Redoxal displayed A3G-dependent restriction, inhibiting viral replication by stabilizing A3G protein levels and increasing A3G in virions. A3G-independent activity was also detected. Treatment with uridine or orotate, intermediates of pyrimidine synthesis, diminished redoxal-induced stabilization of A3G and antiviral activity. These results identify redoxal as an inhibitor of HIV-1 replication and suggest its ability to inhibit pyrimidine biosynthesis suppresses viral replication by augmenting A3G antiviral activity. Topics: Aminobiphenyl Compounds; Antiviral Agents; APOBEC-3G Deaminase; Cells, Cultured; Cytidine Deaminase; Enzyme Inhibitors; HIV-1; Humans; Leukocytes, Mononuclear; Phenazines; Pyrimidines; Virus Replication	2015

Article

Year

Redoxal, an inhibitor of de novo pyrimidine biosynthesis, augments APOBEC3G antiviral activity against human immunodeficiency virus type 1.

Virology, 2015, Volume: 484

APOBEC3G (A3G) is a cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA; deamination-independent mechanisms are also implicated. HIV-1 Vif protein counteracts A3G by inducing its proteasomal degradation. Thus, the Vif-A3G axis is a potential therapeutic target. To identify compounds that inhibit Vif:A3G interaction, a 307,520 compound library was tested in a TR-FRET screen. Two identified compounds, redoxal and lomofungin, inhibited HIV-1 replication in peripheral blood mononuclear cells. Lomofungin activity was linked to A3G, but not pursued further due to cytotoxicity. Redoxal displayed A3G-dependent restriction, inhibiting viral replication by stabilizing A3G protein levels and increasing A3G in virions. A3G-independent activity was also detected. Treatment with uridine or orotate, intermediates of pyrimidine synthesis, diminished redoxal-induced stabilization of A3G and antiviral activity. These results identify redoxal as an inhibitor of HIV-1 replication and suggest its ability to inhibit pyrimidine biosynthesis suppresses viral replication by augmenting A3G antiviral activity.

Topics: Aminobiphenyl Compounds; Antiviral Agents; APOBEC-3G Deaminase; Cells, Cultured; Cytidine Deaminase; Enzyme Inhibitors; HIV-1; Humans; Leukocytes, Mononuclear; Phenazines; Pyrimidines; Virus Replication

2015