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Protein Scaffold‐Based Multimerization of Soluble ACE2 Efficiently Blocks SARS‐CoV‐2 Infection In Vitro and In Vivo

2022; Wiley; Volume: 9; Issue: 27 Linguagem: Inglês

10.1002/advs.202201294

2198-3844

Alişan Kayabölen, Uğur Akcan, Doğancan Özturan, Hivda Ülbeği Polat, Gizem Nur Şahin, Nareg Pinarbasi Degirmenci, Canan Bayraktar, Gizem Söyler, Ehsan Sarayloo, Elif Nurtop, Berna Özer, Gülen Güney-Esken, Tayfun Barlas, Ismail Selim Yildirim, Özlem Doğan, Serçin Karahüseyinoğlu, Nathan A. Lack, Mehmet Kaya, Cem Albayrak, Füsun Can, İhsan Solaroğlu, Tugba Bagcı-Önder,

CAR-T cell therapy research

Soluble ACE2 (sACE2) decoys are promising agents to inhibit SARS-CoV-2, as their efficiency is unlikely to be affected by escape mutations. However, their success is limited by their relatively poor potency. To address this challenge, multimeric sACE2 consisting of SunTag or MoonTag systems is developed. These systems are extremely effective in neutralizing SARS-CoV-2 in pseudoviral systems and in clinical isolates, perform better than the dimeric or trimeric sACE2, and exhibit greater than 100-fold neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag fused to a more potent sACE2 (v1) achieves a sub-nanomolar IC