Optimized ACE2-Fc fusion proteins with picomolar neutralization activity against highly evolved SARS-CoV-2 variants.

ABSTRACT: The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised the efficacy of many authorized monoclonal antibody products. This highlights the need for alternative strategies, especially for vulnerable populations such as immunocompromised individuals. Here, we optimized angiotensin-converting enzyme 2 (ACE2)-Fc fusion proteins by combining three engineering steps: in silico mutagenesis of the S protein binding interface to increase affinity, insertion of a flexible linker to improve protein stability and S protein accessibility, and generation of a tetrameric molecule to maximize avidity. Neutralizing activity was tested against a large panel of pre-Omicron and Omicron pseudoviruses and authentic viruses, including JN.1 and KP.2 variants. Optimized A

SUBMITTER: Abanco F 

PROVIDER: S-EPMC12848771 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature