Molecular dynamics simulations and functional studies reveal that hBD-2 binds SARS-CoV-2 spike RBD and blocks viral entry into ACE2 expressing cells

Zhang, L.; Ghosh, S. K.; Basavarajappa, S. C.; Muller-Greven, J.; Penfield, J.; Brewer, A.; Ramakrishnan, P.; Buck, M.; Weinberg, A.

doi:10.1101/2021.01.07.425621

bioRxiv · 10.1101/2021.01.07.425621

Molecular dynamics simulations and functional studies reveal that hBD-2 binds SARS-CoV-2 spike RBD and blocks viral entry into ACE2 expressing cells

Zhang, L.·Ghosh, S. K.·Basavarajappa, S. C.·Muller-Greven, J.·Penfield, J.·Brewer, A.·Ramakrishnan, P.·Buck, M.·Weinberg, A.

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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 comprehensive in-silico studies 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 IC50 of 2.4{+/-} 0.1 M. 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.

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Zhang, L., Ghosh, S. K., Basavarajappa, S. C., Muller-Greven, J., Penfield, J., Brewer, A., Ramakrishnan, P., Buck, M., Weinberg, A.. 2021-01-07. Molecular dynamics simulations and functional studies reveal that hBD-2 binds SARS-CoV-2 spike RBD and blocks viral entry into ACE2 expressing cells. https://doi.org/10.1101/2021.01.07.425621

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