Publication:
Protein scaffold-based multimerization of soluble ACE2 efficiently blocks SARS-CoV-2 infection in vitro and in vivo

Thumbnail Image

School / College / Institute

Organizational Unit
GRADUATE SCHOOL OF HEALTH SCIENCES
Upper Org Unit
Organizational Unit
Organizational Unit
Organizational Unit
SCHOOL OF MEDICINE
Upper Org Unit

Program

KU Authors

Co-Authors

Ulbegi Polat, Hivda
Yıldırım, İsmail Selim

Publication Date

Language

Embargo Status

NO

Journal Title

Journal ISSN

Volume Title

Alternative Title

Abstract

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 IC50, 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.

Source

Publisher

Wiley

Subject

Chemistry, multidisciplinary, Nanoscience and nanotechnology, Materials science, multidisciplinary

Citation

Has Part

Source

Advanced Science

Book Series Title

Edition

DOI

10.1002/advs.202201294

item.page.datauri

Link

Rights

Copyrights Note

Endorsement

Review

Supplemented By

Referenced By

1

Views

3

Downloads

View PlumX Details