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bioRxiv · 10.1101/2020.08.12.247338

Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection

Wang, C.·Wang, S.·Chen, Y.·Zhao, J.·Han, S.·Zhao, G.·Kang, J.·Liu, Y.·Wang, L.·Wang, X.·Xu, Y.·Huang, Y.·Wang, J.
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Abstract

The ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg-1 of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-acheive memrbane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/247338v1_ufig1.gif" ALT="Figure 1"> View larger version (81K): org.highwire.dtl.DTLVardef@4086baorg.highwire.dtl.DTLVardef@4d239eorg.highwire.dtl.DTLVardef@5d8b76org.highwire.dtl.DTLVardef@16f2581_HPS_FORMAT_FIGEXP M_FIG Graphical Table of Contents C_FIG

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Wang, C., Wang, S., Chen, Y., Zhao, J., Han, S., Zhao, G., Kang, J., Liu, Y., Wang, L., Wang, X., Xu, Y., Huang, Y., Wang, J.. 2020-08-12. Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection. https://doi.org/10.1101/2020.08.12.247338

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