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• W4387079864 abstract "The rapid evolution of variants of SARS-CoV-2 highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses the human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables rapid affinity purification of a dimeric protein by altering the active site to prevent autoproteolytic digestion of a C-terminal His10 epitope tag. In cultured cells, mutant ACE2 competitively inhibits lentiviral vectors pseudotyped with spike from multiple SARS-CoV-2 variants, as well as infectious SARS-CoV-2. Moreover, the protein can be nebulized and retains virus-binding properties. We developed a system for delivery of aerosolized ACE2 to K18-hACE2 mice and demonstrate protection by our modified ACE2 when delivered as a prophylactic agent. These results show proof-of-concept for an aerosolized delivery method to evaluate anti-SARS-CoV-2 agents in vivo and suggest a new tool in the ongoing fight against SARS-CoV-2 and other ACE2-dependent viruses." @default.
• W4387079864 created "2023-09-28" @default.
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• W4387079864 date "2023-09-27" @default.
• W4387079864 modified "2023-10-18" @default.
• W4387079864 title "Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo" @default.
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• W4387079864 doi "https://doi.org/10.1101/2023.09.26.559550" @default.
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