James J Zheng1
Mentors: John S Decker1, Michael D Lynch, MD, PhD1,2
Departments of Biomedical Engineering1, Chemistry2
Lectins are naturally occurring proteins found in bacteria, plants, and algae that recognize specific carbohydrates found on many viral envelope proteins. This unique binding behavior allows these proteins to have broad-spectrum antiviral capabilities, neutralizing viruses such as HIV, influenza, Ebola, and SARS-CoV with varying degrees of activity. While multivalent binding between lectins and glycans has been shown to play a key role in viral neutralization beyond what can be explained by binding avidity alone, the mechanisms linking multivalency and neutralization are not well understood. We believe that lectin crosslinking between different envelope protein domains may inhibit cell-entry-associated conformational changes in viral envelope proteins, resulting in viral neutralization. Using rigid-body protein docking simulations between a subset of lectins and viral envelope proteins found on HIV-1 and H1N1, we compared predicted crosslinking to experimental data on neutralization potency and neutralization-modifying glycan deletions. Hopefully, this analysis will enable us to identify a key mechanism of lectin antiviral activity, providing a robust model for engineering improved broad-spectrum antivirals to counter emerging pandemic viruses such as SARS-CoV-2.