摘要：SummaryNew approaches to complement vaccination are needed to combat the spread of SARS-CoV-2 and stop COVID-19-related deaths and medical complications. Human beta defensin 2 (hBD-2) is a naturally occurring epithelial cell-derived host defense peptide that has anti-viral properties. Our comprehensivein-silicostudies demonstrate that hBD-2 binds the site on the CoV-2-RBD that docks with the ACE2 receptor. Biophysical measurements confirm that hBD-2 indeed binds to the CoV-2-receptor-binding domain (RBD) (KD∼ 2μM by surface plasmon resonance), preventing it from binding to ACE2-expressing cells. Importantly, hBD-2 shows specificity by blocking CoV-2/spike pseudoviral infection, but not VSVG-mediated infection, of ACE2-expressing human cells with an IC50of 2.8 ± 0.4 μM. These promising findings offer opportunities to develop hBD-2 and/or its derivatives and mimetics to safely and effectively use as agents to prevent SARS-CoV-2 infection.Graphical abstractDisplay OmittedHighlights•HBD-2 binds spike-RBD at the ACE2 interaction site in silico•Biophysical and biological assays confirm hBD-2 binding to spike-RBD•HBD-2 blocks spike-RBD:ACE2 binding•HBD-2 prevents CoV-2/spike pseudovirions from infecting ACE2-expressing human cellsTherapeutics; Virology
