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

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.