Lectins as Promising Therapeutics for the Prevention and Treatment of HIV and Other Potential Coinfections

Mazalovska, Milena; Kouokam, J. Calvin

Many enveloped viruses are covered by virally encoded glycoproteins displayed on the surface. In the case of HIV-1, the envelope glycoproteins gp120 and gp41 are heavily glycosylated, and N-linked carbohydrates might make up to 50% of the total molecular weight of gp120 [29] . All the potential 24 N-linked glycosylation sites are utilized in gp120, 13 of which contain complex-type oligosaccharides while 11 primarily comprise high-mannose-type and/or hybrid-type oligosaccharide structures [30, 31] . The associated oligosaccharides contain mannose, galactose, N-acetyl-glucosamine (GlcNAc), Nacetyl-galactosamine (GalNAc), L-fucose, and sialic acid in their branches [31] . The most credible mechanism proposed for virus-cell attachment involves the interaction between positively charged regions of the viral-envelope glycoproteins and negatively charged heparan sulphate proteoglycans. The fusion process starts with binding of gp120 to the cell-surface CD4 antigen. These entry events are vulnerable to agents that specifically and strongly interact with the glycans since they may disturb the association of viral envelope proteins with host cell receptors, that is, gp120 and CD4, respectively [18, 32] . It is believed that these agents alter the efficient interaction between gp120 (or gp41) and its (co)receptors through steric hindrance, prevention of necessary conformational changes of env, and/or cross-linking of several glycans present on env and/or the target cell [33] . Lectins, which are carbohydrate-binding proteins, possess such binding properties. Indeed, sound anti-HIV effects are attributed to lectins with specific recognition for mannose (Man) and/or GlcNAc [8, 33] . A number of plant and microbial lectins have been researched in recent years, including griffithsin (GRFT), actinohivin (AH), concanavalin-A (ConA), cyanovirin-N (CV-N), microvirin (MVN), and banana lectin (BanLec). Generally speaking, these lectins contain multiple sugarbinding sites allowing them to form multivalent interactions with gp120. Such interactions confer to lectins the ability to neutralize a broad range of lab-adapted and clinically isolated strains of HIV-1 and HIV-2. The following are a few examples of lectins that have been investigated for their antiretroviral activities.