O-Methylviridicatin (Synonyms: AIDS-089094,3-methoxy-4-phenyl-Carbostyril,Viridicatin methyl ester)

IC50: 2.5 μM: inhibits virus production in OM-10.1 cells (HL-60 promyelocytes infected with HIV-1) treated with TNF-α.

5 μM: blocks activation of the HIV long terminal repeat by TNF-α in HeLa cells

O-Methylviridicatin, a natural derivative of the alkaloid mycotoxin viridicatin, is produced by several species in the genus, Penicillium. It is demonstrated that O-Methylviridicatin, as an inhibitor, blocks the tumor necrosis factor alpha (TNFα)-induced replication of human immunodeficiency virus (HIV). TNFα increases the binding of the cellular transcription factor NF-κB to the HIV long terminal repeat (LTR), which directly triggers transcription of the latent provirus.

In vitro: O-Methylviridicatin had an inhibitory effect on the TNFα-triggered replication of HIV LTR in HeLa cells. In addition, O-Methylviridicatin dose-dependently dampened virus production in the OM-10.1 cell line, which was measured by the output of p24 core antigen into the culture medium. It was demonstrated that the suppressive effect of O-Methylviridicatin was not reversed even if the concentration of TNFα was increased 10-fold [1].

In vivo: Up to now, in vitro study of O-Methylviridicatin is still in the development stage.

Reference:
[1].  Heguy, A., Cai, P., Meyn, P., Houck, D., Russo, S., & Michitsch, R. et al. Isolation and Characterization of the Fungal Metabolite 3-O-Methylviridicatin as an Inhibitor of Tumour Necrosis Factor-Induced Human Immunodeficiency Virus Replication. Antiviral Chemistry and Chemotherapy. 1998; 9(2): 149-155.