A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection

Abstract Approaches are needed for therapy of the severe acute respiratory syndrome from SARS-CoV-2 coronavirus (COVID-19). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviru...

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Autores principales:	Ami Miller, Adam Leach, Jemima Thomas, Craig McAndrew, Emma Bentley, Giada Mattiuzzo, Lijo John, Ali Mirazimi, Gemma Harris, Nadisha Gamage, Stephen Carr, Hanif Ali, Rob Van Montfort, Terence Rabbitts
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5567762413e2437998e17b082de79177
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spelling	oai:doaj.org-article:5567762413e2437998e17b082de791772021-12-02T16:49:37ZA super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection10.1038/s41598-021-89957-z2045-2322https://doaj.org/article/5567762413e2437998e17b082de791772021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89957-zhttps://doaj.org/toc/2045-2322Abstract Approaches are needed for therapy of the severe acute respiratory syndrome from SARS-CoV-2 coronavirus (COVID-19). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2, coupled to the human immunoglobulin γ1 Fc region, using a self-assembling, tetramerization domain from p53 protein. This high molecular weight Quad protein (ACE2-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein and can form a complex with the spike protein plus anti-viral antibodies. The ACE2-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection with greatly enhanced efficacy. The ACE2 tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19. In contrast to monoclonal antibodies, ACE2 decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 receptor.Ami MillerAdam LeachJemima ThomasCraig McAndrewEmma BentleyGiada MattiuzzoLijo JohnAli MirazimiGemma HarrisNadisha GamageStephen CarrHanif AliRob Van MontfortTerence RabbittsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ami Miller Adam Leach Jemima Thomas Craig McAndrew Emma Bentley Giada Mattiuzzo Lijo John Ali Mirazimi Gemma Harris Nadisha Gamage Stephen Carr Hanif Ali Rob Van Montfort Terence Rabbitts A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection
description	Abstract Approaches are needed for therapy of the severe acute respiratory syndrome from SARS-CoV-2 coronavirus (COVID-19). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2, coupled to the human immunoglobulin γ1 Fc region, using a self-assembling, tetramerization domain from p53 protein. This high molecular weight Quad protein (ACE2-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein and can form a complex with the spike protein plus anti-viral antibodies. The ACE2-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection with greatly enhanced efficacy. The ACE2 tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19. In contrast to monoclonal antibodies, ACE2 decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 receptor.
format	article
author	Ami Miller Adam Leach Jemima Thomas Craig McAndrew Emma Bentley Giada Mattiuzzo Lijo John Ali Mirazimi Gemma Harris Nadisha Gamage Stephen Carr Hanif Ali Rob Van Montfort Terence Rabbitts
author_facet	Ami Miller Adam Leach Jemima Thomas Craig McAndrew Emma Bentley Giada Mattiuzzo Lijo John Ali Mirazimi Gemma Harris Nadisha Gamage Stephen Carr Hanif Ali Rob Van Montfort Terence Rabbitts
author_sort	Ami Miller
title	A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection
title_short	A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection
title_full	A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection
title_fullStr	A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection
title_full_unstemmed	A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection
title_sort	super-potent tetramerized ace2 protein displays enhanced neutralization of sars-cov-2 virus infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5567762413e2437998e17b082de79177
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A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection

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