Evidence map›Paper›PMID 32766586›Full record

ArticlebioRxiv : the preprint server for biology2020

Engineered ACE2 receptor traps potently neutralize SARS-CoV-2.

Anum Glasgow, Jeff Glasgow, Daniel Limonta, Paige Solomon, Irene Lui, Yang Zhang, Matthew A Nix, Nicholas J Rettko, Shion A Lim, Shoshana Zha and 10 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 38 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 2 countries.

Anum GlasgowDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, CA.
Jeff GlasgowDepartment of Pharmaceutical Chemistry, University of California at San Francisco, CA.
Daniel LimontaLi Ka Shing Institute of Virology, University of Alberta, Edmonton, Canada.
Paige SolomonDepartment of Pharmaceutical Chemistry, University of California at San Francisco, CA.
Irene LuiDepartment of Pharmaceutical Chemistry, University of California at San Francisco, CA.
Yang ZhangDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, CA.
Matthew A NixDepartment of Laboratory Medicine, University of California at San Francisco, CA.
Nicholas J RettkoDepartment of Pharmaceutical Chemistry, University of California at San Francisco, CA.
Shion A LimDepartment of Pharmaceutical Chemistry, University of California at San Francisco, CA.
Shoshana ZhaDepartment of Medicine, University of California at San Francisco, CA.
Rachel YaminLaboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY.
Kevin KaoLaboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY.
Oren S RosenbergDepartment of Medicine, University of California at San Francisco, CA.
Jeffrey V RavetchLaboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY.
Arun P WiitaDepartment of Laboratory Medicine, University of California at San Francisco, CA.
Kevin K LeungDepartment of Pharmaceutical Chemistry, University of California at San Francisco, CA.
Xin X ZhouDepartment of Pharmaceutical Chemistry, University of California at San Francisco, CA.
Tom C HobmanLi Ka Shing Institute of Virology, University of Alberta, Edmonton, Canada.
Tanja KortemmeDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, CA.
James A WellsDepartment of Pharmaceutical Chemistry, University of California at San Francisco, CA.
University of California, San Francisco · USRockefeller University · USUniversity of Alberta · CA

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
Understanding B cell memory in response to diverse virus infectionsU19AI111825 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 2014 to 2023
$26.0M
RESEARCH TRAINING IN CHEMISTRY AND CHEMICAL BIOLOGYT32GM064337 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT · 2002 to 2021
$7.8M
Mapping and rewiring protein allosteryK99GM135529 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GLASGOW, ANUM AZAM · 2020 to 2021
$194k
NCI NIH HHS P30 CA082103NIAID NIH HHS U19 AI111825NIGMS NIH HHS K99 GM135529NIGMS NIH HHS T32 GM064337
6 · The paper itself

Abstract

An essential mechanism for SARS-CoV-1 and -2 infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). Here we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human Fc domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2 pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50) in the 10-100 ng/ml range. Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-utilizing coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be predesigned for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies isolated or generated from convalescent patients.

Identifiers

PMID32766586
PMCPMC7402043
OpenAlexW3046380953

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.