1. A tetrameric ACE2 protein broadly neutralizes SARS-CoV-2 spike variants of concern with elevated potency.
- Author
-
Leach, Adam, Ilca, F. Tudor, Akbar, Zulaikha, Ferrari, Mathieu, Bentley, Emma M., Mattiuzzo, Giada, Onuoha, Shimobi, Miller, Ami, Ali, Hanif, and Rabbitts, Terence H.
- Subjects
- *
SARS-CoV-2 , *MONOCLONAL antibodies , *COVID-19 pandemic , *ANGIOTENSIN receptors , *COVID-19 , *THERAPEUTICS , *VIRAL antibodies - 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. • Soluble ACE2 coronavirus receptor neutralizes SARS-CoV-2 infection. • SARS-CoV-2 neutralization is enhanced by tetramerization of ACE2. • Tetrameric ACE2 is more potent than a dimeric form. • SARS-CoV-2 variants of concern are neutralized by tetrameric ACE2. • Tetrameric ACE2 decoy protein could be used in future, new coronavirus pandemics. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF