Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig


Corresponding author: Shi Hu

Affiliations: Second Military Medical University

Publication date: this article was published online on April 24, 2020

DOI: http://doi.org/10.1038/s41467-020-16048-4

Highlights

The researchers generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, they also demonstrated that the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro.

Nomination Reason

This work reveals that an ACE2-Ig exhibit cross-reactivity against coronaviruses, and have potential applications in the diagnosis, prophylaxis, and treatment of SARS-CoV-2.

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110 Reply

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis, and treat


Clinical development is urgent!

All of the paper is very good!


I can share this paper:/10.1080/19420862.2020.1804241


I think ACE2-Fc is the best anti-virus antibody-lile molecular. It is not only bindings to SARS-CoV-2, and many in the future to bind a unkown pathgen


Yes. I think so. why there is no information for clinical development?

All the paper is very interesting!


Also for this :Chan K K, Dorosky D, Sharma P, et al. Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2[J]. Science, 2020, 369(6508): 1261-1265.


Is it nessary to find a binding enhencer?what about the virus mutation?

This work is very good too. This is of interested.

I recomment this preprint:10.1101/2020.03.16.994236:The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S binds ACE2 on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedente


Is there any chance to sceen a smal molecular weigh peptide to act like ace2?


The half life of peptide may be short that whole protein.

I think this is a good idea.

View more replies 2 Replies

For reference:Li Y, Wang H, Tang X, et al. Potential host range of multiple SARS-like coronaviruses and an improved ACE2-Fc variant that is potent against both SARS-CoV-2 and SARS-CoV-1[J]. bioRxiv, 2020.


Is there any other receptors reported for SARS-COV-2?

I copyed the abstrct:"We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor. Additionally, we optimize algorithms for protein glycosylation modelling in order to expedite future model development. All models and algorithms are openly available."

View more replies 4 Replies

an other ref:Bernardi A, Huang Y, Harris B, et al. Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain[J]. PloS one, 2020, 15(8): e0237295.

Thanks for share. very useful!

Iwanaga N, Cooper L, Rong L, et al. Novel ACE2-IgG1 fusions with improved activity against SARS-CoV2[J]. bioRxiv, 2020.

does this improved ACE2 protein have better activity?

This work is very inteseting!


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