Open AccessProtein Scaffold‐Based Multimerization of Soluble ACE2 Efficiently Blocks SARS‐CoV‐2 Infection In Vitro and In Vivo
Author(s) -
Kayabolen Alisan,
Akcan Ugur,
Özturan Doğancan,
UlbegiPolat Hivda,
Sahin Gizem Nur,
PinarbasiDegirmenci Nareg,
Bayraktar Canan,
Soyler Gizem,
Sarayloo Ehsan,
Nurtop Elif,
Ozer Berna,
GuneyEsken Gulen,
Barlas Tayfun,
Yildirim Ismail Selim,
Dogan Ozlem,
Karahuseyinoglu Sercin,
Lack Nathan A.,
Kaya Mehmet,
Albayrak Cem,
Can Fusun,
Solaroglu Ihsan,
BagciOnder Tugba
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202201294
Subject(s) - in vivo , covid-19 , neutralization , potency , monoclonal antibody , in vitro , ic50 , chemistry , virology , antibody , microbiology and biotechnology , biology , biochemistry , virus , medicine , immunology , infectious disease (medical specialty) , disease , genetics , pathology , outbreak
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 50 , comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutations for variants of concern, including delta and omicron, are also neutralized efficiently with multimeric sACE2. Finally, therapeutic treatment of sACE2(v1)‐MoonTag provides protection against SARS‐CoV‐2 infection in an in vivo mouse model. Therefore, highly potent multimeric sACE2 may offer a promising treatment approach against SARS‐CoV‐2 infections.