Linear biocompatible mannosylated PAAs as potential broad-spectrum microbicides for sexually transmitted diseases

Interactions between viral proteins and cellular receptors mediate the initial steps of viral infections. Blocking the host receptors with high-affinity ligands may prevent viral adhesion and stop the infection process. We already demonstrated that mannosylated glycodendrimers are able to specifically block DC-SIGN, a C-type lectin receptor that mediates human immunodeficiency virus (HIV) infection. In addition, an amphoteric, but prevailingly cationic polyamidoamine (PAA), named AGMA1, proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2, whilst an amphoteric, but prevailingly anionic PAA, named ISA23, proved inactive. Here we show that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, preserves the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity, thus providing broad-spectrum, dual action mode, viral infection inhibitors.