CryoEM Based Models for Adenovirus Neutralization by Human Alpha-Defensin 5

Defensins are peptides of the innate immune system with potent antimicrobial activity. Despite strong interest in defensins as potential pharmaceutical compounds, commercial development of these peptides has been challenging. New generations of modified antimicrobial peptides are being pursued to improve their potential as pharmaceuticals. Strategies include peptide mimetics, hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates and immobilized peptides [1]. Our laboratories have been working on understanding the molecular mechanisms of defensins against adenovirus to characterize key interaction sites. There are six human alpha-defensins, including HD5, and multiple beta-defensins. Defensin action against enveloped viruses includes membrane disruption, as well as interference with viral membrane fusion. Alpha-defensins also neutralize viruses that lack envelopes including human adenovirus (HAdV), human papillomavirus (HPV), and polyomaviruses.