1. Molecular dynamics simulations and functional studies reveal that hBD-2 binds SARS-CoV-2 spike RBD and blocks viral entry into ACE2 expressing cells
- Author
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Matthias Buck, Liqun Zhang, Santosh K. Ghosh, Aaron Weinberg, Jackson Penfield, Jeannine Muller-Greven, Shrikanth C. Basavarajappa, Ann Brewer, and Parameswaran Ramakrishnan
- Subjects
chemistry.chemical_classification ,Coronavirus disease 2019 (COVID-19) ,Chemistry ,SARS-CoV-2 ,Beta-defensin 2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,Peptide ,Epithelium ,Article ,Cell biology ,medicine.anatomical_structure ,Viral entry ,receptor binding domain (RBD) ,medicine ,Receptor ,ACE2 receptor ,Binding domain ,Human beta defensin-2 (hBD-2) - Abstract
New approaches to complement vaccination are needed to combat the spread of SARS-CoV-2 and stop COVID-19 related deaths and long-term medical complications. Human beta defensin 2 (hBD-2) is a naturally occurring epithelial cell derived host defense peptide that has antiviral properties. Our comprehensivein-silicostudies demonstrate that hBD-2 binds the site on the CoV-2-RBD that docks with the ACE2 receptor. Biophysical and biochemical assays confirm that hBD-2 indeed binds to the CoV-2-receptor binding domain (RBD) (KD∼ 300 nM), preventing it from binding to ACE2 expressing cells. Importantly, hBD-2 shows specificity by blocking CoV-2/spike pseudoviral infection, but not VSV-G mediated infection, of ACE2 expressing human cells with an IC50of 2.4± 0.1 μM. These promising findings offer opportunities to develop hBD-2 and/or its derivatives and mimetics to safely and effectively use as novel agents to prevent SARS-CoV-2 infection.
- Published
- 2021