About: Novel ACE2-IgG1 fusions with improved activity against SARS-CoV2

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About: Novel ACE2-IgG1 fusions with improved activity against SARS-CoV2 Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Novel ACE2-IgG1 fusions with improved activity against SARS-CoV2
Creator	Rong, Lijun Crabtree, Jackelyn Kolls, Jay Tripp, Ralph Beddingfield, Brandon Cooper, Laura Iwanaga, Naoki
Source	BioRxiv; Medline; PMC
abstract	SARS-CoV2, the etiologic agent of COVID-19, uses ACE2 as a cell entry receptor. Soluble ACE2 has been shown to have neutralizing antiviral activity but has a short half-life and no active transport mechanism from the circulation into the alveolar spaces of the lung. To overcome this, we constructed an ACE2-human IgG1 fusion protein with mutations in the catalytic domain of ACE2. This fusion protein contained a LALA mutation that abrogates Fcrγ binding, but retains FcRN binding to prolong the half-life, as well as achieve therapeutic concentrations in the lung lavage. Interestingly, a mutation in the catalytic domain of ACE2, MDR504, completely abrogated catalytic activity, but significantly increased binding to SARS-CoV2 spike protein in vitro. This feature correlated with more potent viral neutralization in a plaque assay. Parental administration of the protein showed stable serum concentrations with a serum half-life of ~ 145 hours with excellent bioavailability in the epithelial lining fluid of the lung. These data support that the MDR504 hACE2-Fc is an excellent candidate for pre or post-exposure prophylaxis or treatment of COVID-19.
has issue date	2020-06-15(xsd:dateTime)
bibo:doi	10.1101/2020.06.15.152157
bibo:pmid	32587964
has license	cc-by-nc-nd
sha1sum (hex)	80182e5c15fc88fe7d6aebbbaa6b8f7dbaa7d6de
schema:url	https://doi.org/10.1101/2020.06.15.152157
resource representing a document's title	Novel ACE2-IgG1 fusions with improved activity against SARS-CoV2
has PubMed Central identifier	PMC7310620
has PubMed identifier	32587964
schema:publication	bioRxiv
resource representing a document's body	covid:80182e5c15fc88fe7d6aebbbaa6b8f7dbaa7d6de#body_text
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