1. Protein Scaffold-Based Multimerization of Soluble ACE2 Efficiently Blocks SARS-CoV-2 Infection In Vitro and In Vivo
- Author
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Alisan Kayabolen, Ugur Akcan, Doğancan Özturan, Hivda Ulbegi‐Polat, Gizem Nur Sahin, Nareg Pinarbasi‐Degirmenci, Canan Bayraktar, Gizem Soyler, Ehsan Sarayloo, Elif Nurtop, Berna Ozer, Gulen Guney‐Esken, Tayfun Barlas, Ismail Selim Yildirim, Ozlem Dogan, Sercin Karahuseyinoglu, Nathan A. Lack, Mehmet Kaya, Cem Albayrak, Fusun Can, Ihsan Solaroglu, Tugba Bagci‐Onder, ALBAYRAK, CEM, Kayabölen, Alişan, Akcan, Uğur, Özturan, Doğancan, Sahin, Gizem Nur, Pınarbaşı Değirmenci, Nareğ, Bayraktar, Canan, Soyler, Gizem, Sarayloo, Ehsan, Nurtop, Elif, Özer, Berna, Güney Esken, Gülen, Barlas, Tayfun, Doğan, Özlem (ORCID 0000-0002-6505-4582 & YÖK ID 170418), Karahüseyinoğlu, Serçin (ORCID 0000-0001-5531-2587 & YÖK ID 110772), Lack, Nathan Alan (ORCID 0000-0001-7399-5844 & YÖK ID 120842), Kaya, Mehmet, Albayrak, Cem, Can, Füsun (ORCID 0000-0001-9387-2526 & YÖK ID 103165), Solaroğlu, İhsan (ORCID 0000-0002-9472-1735 & YÖK ID 102059), Önder, Tuğba Bağcı (ORCID 0000-0003-3646-2613 & YÖK ID 184359), Ulbegi Polat, Hivda, Yıldırım, İsmail Selim, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), Koç University Hospital, Graduate School of Health Sciences, and School of Medicine
- Subjects
Kayabolen A., Akcan U., Ozturan D., Ulbegi-Polat H., Sahin G. N. , Pinarbasi-Degirmenci N., Bayraktar C., Soyler G., Sarayloo E., Nurtop E., et al., -Protein Scaffold-Based Multimerization of Soluble ACE2 Efficiently Blocks SARS-CoV-2 Infection In Vitro and In Vivo-, ADVANCED SCIENCE, 2022 ,SARS-CoV-2 ,General Chemical Engineering ,General Engineering ,General Physics and Astronomy ,Medicine (miscellaneous) ,Antibodies, Monoclonal ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,COVID-19 Drug Treatment ,Mice ,Animals ,General Materials Science ,Angiotensin-Converting Enzyme 2 ,Decoy receptors ,Escape mutations ,MoonTag ,Multimerization ,Neutralization ,sACE2 ,SunTag ,Chemistry, multidisciplinary ,Nanoscience and nanotechnology ,Materials science, multidisciplinary - 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., Koç University Isbank Center for Infectious Diseases (KUISCID); Koç University Research Center for Transla-tional Medicine (KUTTAM)
- Published
- 2022