Antiviral Res . A tetrameric ACE2 protein broadly neutralizes SARS-CoV-2 spike variants of concern with elevated potency

[tetano]

Antiviral Res


. 2021 Aug 7;105147.
doi: 10.1016/j.antiviral.2021.105147. Online ahead of print.
A tetrameric ACE2 protein broadly neutralizes SARS-CoV-2 spike variants of concern with elevated potency


Adam Leach ¹ , F Tudor Ilca ² , Zulaikha Akbar ² , Mathieu Ferrari ² , Emma M Bentley ³ , Giada Mattiuzzo ³ , Shimobi Onuoha ² , Ami Miller ¹ , Hanif Ali ⁴ , Terence H Rabbitts ⁵



Affiliations

• PMID: 34375715
• DOI: 10.1016/j.antiviral.2021.105147

Abstract

The SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) was previously engineered into a high affinity tetravalent format (ACE2-Fc-TD) that is a potential decoy protein in SARS-CoV-2 infection.We report that this protein shows greatly enhanced binding to SARS-CoV-2 spike proteins of the SARS-CoV-2 variants of concern B.1.1.7 (alpha variant, originally isolated in the United Kingdom) and B.1.351 (beta variant, originally isolated in South Africa) with picomolar compared with nanomolar Kd values. In addition, ACE2-Fc-TD displays greater neutralization of SARS-CoV-2 pseudotype viruses compared to a dimeric ACE2-Fc, with enhanced activity on variant B.1.351. This tetrameric decoy protein would be a valuable addition to SARS-CoV-2 therapeutic approaches, especially where vaccination cannot be used but also should there be any future coronavirus pandemics.

Keywords: ACE2; COVID-19; Coronavirus; SAR2-CoV-2; Spike protein; VOC; Variant spike.