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BioengineeringbioRxiv
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ACE2-Coated Virus-Like Particles Effectively Block SARS-CoV-2 Infection

C. Bayraktar, A. Kayabolen, A. Odabas, A. Durgun, I. Kok, K. Sevinc, A. Supramaniam, A. Idris, T. Bagci-Onder

Abstract

A large body of research accumulated over the past three years dedicated to our understanding and fighting COVID-19. Blocking the interaction between SARS-CoV-2 Spike and ACE2 receptor has been considered an effective strategy as anti-SARS-CoV-2 therapeutics. In this study, we developed ACE2-coated virus-like particles (ACE2-VLPs), which can be utilized to prevent viral entry into host cells and efficiently neutralize the virus. These ACE2-VLPs exhibited high neutralization capacity even when applied at low doses, and displayed superior efficacy compared to extracellular vesicles carrying ACE2, in the in vitro pseudoviral assays. ACE2-VLPs were stable under different environmental temperatures, and they were effective in blocking all tested variants of concern in vitro. Finally, ACE2-VLPs displayed marked neutralization capacity against Omicron BA.1 in the Vero E6 cells. Based on their superior efficacy compared to extracellular vesicles, and their demonstrated success against live virus, ACE2-VLPs can be considered as vital candidates for treating SARS-CoV-2. This novel therapeutic approach of VLP coating with receptor particles can serve as proof-of-concept for designing effective neutralization strategies for other viral diseases in the future. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/558424v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@30ac94org.highwire.dtl.DTLVardef@1926217org.highwire.dtl.DTLVardef@165d9f0org.highwire.dtl.DTLVardef@1c737f9_HPS_FORMAT_FIGEXP M_FIG In our study, we demonstrate the prevention of SARS-CoV-2 infection through the use of Ace2-coated VLPs. C_FIG

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