Evidence map›Paper›PMID 35982665›Full record

ArticlebioRxiv : the preprint server for biology2022

Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps.

Soumya G Remesh, Gregory E Merz, Axel F Brilot, Un Seng Chio, Alexandrea N Rizo, Thomas H Pospiech, Irene Lui, Mathew T Laurie, Jeff Glasgow, Chau Q Le and 16 more

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

Article in bioRxiv : the preprint server for biology, 2022. 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, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 2 institutions in 1 country.

Soumya G RemeshDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA - 94158, USA.
Gregory E MerzQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Axel F BrilotQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Un Seng ChioQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Alexandrea N RizoQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Thomas H PospiechQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Irene LuiDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA - 94158, USA.
Mathew T LaurieDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA - 94158, USA.
Jeff GlasgowDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA - 94158, USA.
Chau Q LeDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA - 94158, USA.
Yun ZhangDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA - 94158, USA.
Devan DiwanjiQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Evelyn HernandezQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Jocelyne LopezQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Komal Ishwar PawarQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Sergei PourmalQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Amber M SmithQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Fengbo ZhouQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
QCRG Structural Biology Consortium
Joseph DeRisiDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA - 94158, USA.
Tanja KortemmeQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Oren S RosenbergQBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA - 94158, USA.
Anum GlasgowDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Kevin K LeungDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA - 94158, USA.
James A WellsDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA - 94158, USA.
Kliment A VerbaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA - 94158, USA.
University of California, San Francisco · USColumbia University · US

Funding

Surfaceomic technologies and antibodies to probe cell surface proteomes and their interactomes at unprecedented small scale and high-resolutionR35GM122451 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES A WELLS · 2017 to 2026
$5.3M
Mapping and rewiring protein allosteryK99GM135529 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GLASGOW, ANUM AZAM · 2020 to 2021
$194k
NIGMS NIH HHS K99 GM135529NIGMS NIH HHS R35 GM122451
6 · The paper itself

Abstract

The SARS-CoV-2 Omicron variant, with 15 mutations in Spike receptor binding domain (Spike-RBD), renders virtually all clinical monoclonal antibodies against WT SARS-CoV-2 ineffective. We recently engineered the SARS-CoV-2 host entry receptor, ACE2, to tightly bind WT-Spike-RBD and prevent viral entry into host cells ("receptor traps"). Here we determine cryo-EM structures of our receptor traps in complex with full length Spike. We develop a multi-model pipeline combining Rosetta protein modeling software and cryo-EM to allow interface energy calculations even at limited resolution and identify interface side chains that allow for high affinity interactions between our ACE2 receptor traps and Spike-RBD. Our structural analysis provides a mechanistic rationale for the high affinity (0.53 - 4.2nM) binding of our ACE2 receptor traps to Omicron-RBD confirmed with biolayer interferometry measurements. Finally, we show that ACE2 receptor traps potently neutralize Omicron- and Delta-pseudotyped viruses, providing alternative therapeutic routes to combat this evolving virus.

Identifiers

PMID35982665
PMCPMC9387132
OpenAlexW4290987242

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.