HBD-2 binds SARS-CoV-2 RBD and blocks viral entry: Strategy to combat COVID-19
Liqun Zhang, Santosh K. Ghosh, Shrikanth Chomanahalli Basavarajappa, Yinghua Chen, Pravesh Shrestha, Jackson Penfield, Ann M. Brewer, Parameswaran Ramakrishnan, Matthias Buck, Aaron Weinberg
Abstract
New 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 comprehensive in-silico studies 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) (K D ∼ 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 IC 50 of 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.