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Full-Text Articles in Medicine and Health Sciences
A Computationally Designed Ace2 Decoy Has Broad Efficacy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam
A Computationally Designed Ace2 Decoy Has Broad Efficacy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam
SKMC Student Presentations and Publications
SARS-CoV-2, especially B.1.1.529/omicron and its sublineages, continues to mutate to evade monoclonal antibodies and antibodies elicited by vaccination. Affinity-enhanced soluble ACE2 (sACE2) is an alternative strategy that works by binding the SARS-CoV-2 S protein, acting as a 'decoy' to block the interaction between the S and human ACE2. Using a computational design strategy, we designed an affinity-enhanced ACE2 decoy, FLIF, that exhibited tight binding to SARS-CoV-2 delta and omicron variants. Our computationally calculated absolute binding free energies (ABFE) between sACE2:SARS-CoV-2 S proteins and their variants showed excellent agreement to binding experiments. FLIF displayed robust therapeutic utility against a broad range …