A glycosylated HIV microbicide based on N6

Pegylated Griffithsin -- an "early model"  (5/10/16) 

Lectins like griffithsin have received some interest as potential HIV microbicides where binding the HIV particle’s glycan coat with lectins might act to prevent infection. Griffithsin binds mannose moieties. All female reproductive tract epithelia express the mucin MUC1, and MUC1 has N-linked glycosylation that results in a glycan coat which may have mannose moieties. So mannose binding lectins like griffithsin may just as easily bind mucus proteins as HIV and be prevented from reaching their target. We might want something that binds HIV more specifically.

One possible design is a glycosylated neutralizer based on the N6 antibody, an antibody that has been shown to effectively neutralize 98% of 181 different HIV isolates that it was tested against. The N6 antibody has the property that it binds the CD4 binding site on HIV's gp120 protein mostly with one chain -- the heavy chain. The light chain has evolved to stay out of the way. This allows the majority of the antibody to be cut away leaving a small molecule with the expectation that this molecule might still bind the CD4 binding site just fine.

Some of the strongest phenotypic properties of HIV's Env structure linked to sexual transmission are shorter hypervariable domains and fewer potential N-linked glycosylation sites. A reduction in glycosylation sites could be supporting viral entry for a variety of reasons, so to preserve the presentation of a dense glycan coat, it might be desirable for a protein based neutralizer, such as the design proposed above to have a dense glycan coat of it's own. This should also improve the solubility of the neutralizer.

Here is an idea of what these molecules might be like.