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

Autor: Leach A; Institute of Cancer Research, Centre for Cancer Drug Discovery, 15 Cotswold Road, Sutton, London, SM2 5NG, UK., Ilca FT; Autolus Therapeutics Plc, 58 Wood Lane, London, W12 7RZ, UK., Akbar Z; Autolus Therapeutics Plc, 58 Wood Lane, London, W12 7RZ, UK., Ferrari M; Autolus Therapeutics Plc, 58 Wood Lane, London, W12 7RZ, UK., Bentley EM; National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK., Mattiuzzo G; National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK., Onuoha S; Autolus Therapeutics Plc, 58 Wood Lane, London, W12 7RZ, UK., Miller A; Institute of Cancer Research, Centre for Cancer Drug Discovery, 15 Cotswold Road, Sutton, London, SM2 5NG, UK., Ali H; Quadrucept Limited, 1010 Cambourne Road, Cambridge, CB23 6DW, UK., Rabbitts TH; Institute of Cancer Research, Centre for Cancer Drug Discovery, 15 Cotswold Road, Sutton, London, SM2 5NG, UK. Electronic address: terry.rabbitts@icr.ac.uk.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2021 Oct; Vol. 194, pp. 105147. Date of Electronic Publication: 2021 Aug 08.
DOI: 10.1016/j.antiviral.2021.105147
Abstrakt: 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.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE
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