Anti-HIV-1 activity of a tripodal receptor that recognizes mannose oligomers

• Compound 1 inhibits the replication of HIV-1 in the low micromolar range.
• Compound 1 binds pronouncedly with HIV envelope glycoprotein gp120.
• Compound 1 has HIV-1 integrase (IN) inhibitory capacity.
• Gp120 binding rather than IN inhibition seems to be the primary mechanism of antiviral activity of 1.

The glycoprotein gp120 of the HIV-1 viral envelope has a high content in mannose residues, particularly α-1,2-mannose oligomers. Compounds that interact with these high-mannose type glycans may disturb the interaction between gp120 and its (co)receptors and are considered potential anti-HIV agents. Previously, we demonstrated that a tripodal receptor (1), with a central scaffold of 1,3,5-triethylbenzene substituted with three 2,3,4-trihydroxybenzoyl groups, selectively recognizes α-1,2-mannose polysaccharides. Here we present additional studies to determine the anti-HIV-1 activity and the mechanism of antiviral activity of this compound. Our studies indicate that 1 shows anti-HIV-1 activity in the low micromolar range and has pronounced gp120 binding and HIV-1 integrase inhibitory capacity. However, gp120 binding rather than integrase inhibition seems to be the primary mechanism of antiviral activity of 1.

Figure optionsDownload as PowerPoint slide