Evidence map›Paper›PMID 33526471›Full record

ArticleJournal of the American Society of Nephrology : JASN2021

A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids.

Jan Wysocki, Minghao Ye, Luise Hassler, Ashwani Kumar Gupta, Yuguo Wang, Vlad Nicoleascu, Glenn Randall, Jason A Wertheim, Daniel Batlle

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 96 citations in OpenAlex.

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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Jan WysockiDivision of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Minghao YeDivision of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Luise HasslerDivision of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Ashwani Kumar GuptaComprehensive Transplant Center, Department of Surgery, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois.ORCID 0000-0001-7069-5299
Yuguo WangComprehensive Transplant Center, Department of Surgery, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Vlad NicoleascuDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, Illinois.
Glenn RandallDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, Illinois.
Jason A WertheimComprehensive Transplant Center, Department of Surgery, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois.ORCID 0000-0001-5680-1067
Daniel BatlleDivision of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Northwestern University · USUniversity of Chicago · US

Funding

Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
Therapeutics Development Core (Core B)P30DK114857 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GEORGE, ALFRED L., QUAGGIN, SUSAN E. · 2018 to 2022
$5.7M
Urinary Renin Angiotensin System in DiabetesR01DK104785 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BATLLE, DANIEL · 2015 to 2017
$939k
NCATS NIH HHS UL1 TR001422NIDDK NIH HHS R01 DK104785
6 · The paper itself

Abstract

backgroundThere is an urgent need for approaches to prevent and treat SARS-CoV-2 infection. Administration of soluble ACE2 protein acting as a decoy to bind to SARS-CoV-2 should limit viral uptake mediated by binding to membrane-bound full-length ACE2, and further therapeutic benefit should result from ensuring enzymatic ACE2 activity to affected organs in patients with COVID-19.

methodsA short variant of human soluble ACE2 protein consisting of 618 amino acids (hACE2 1-618) was generated and fused with an albumin binding domain (ABD) using an artificial gene encoding ABDCon, with improved albumin binding affinity. Human kidney organoids were used for infectivity studies of SARS-CoV-2 in a BSL-3 facility to examine the neutralizing effect of these novel ACE2 variants.

resultsWhereas plasma ACE2 activity of the naked ACE2 1-618 and ACE2 1-740 lasted about 8 hours, the ACE2 1-618-ABD resulted in substantial activity at 96 hours, and it was still biologically active 3 days after injection. Human kidney organoids express ACE2 and TMPRSS2, and when infected with SARS-CoV-2, our modified long-acting ACE2 variant neutralized infection.

conclusionsThis novel ACE2 1-618-ABD can neutralize SARS-CoV-2 infectivity in human kidney organoids, and its prolonged duration of action should ensure improved efficacy to prevent viral escape and dosing convenience.

Indexed as

ACE2ACE2 1-618-ABDACE2 decoyCOVID-19organoidsSARS-CoV-2soluble ACE2 proteins

Identifiers

PMID33526471
PMCPMC8017551
OpenAlexW3126773380

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.