Evidence map›Paper›PMID 33836016›Full record

ArticlePLoS pathogens2021

Mutations derived from horseshoe bat ACE2 orthologs enhance ACE2-Fc neutralization of SARS-CoV-2.

Huihui Mou, Brian D Quinlan, Haiyong Peng, Guanqun Liu, Yan Guo, Shoujiao Peng, Lizhou Zhang, Meredith E Davis-Gardner, Matthew R Gardner, Gogce Crynen and 8 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

49 citing papers in PubMed, 138 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 1 country.

Huihui MouDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.ORCID 0000-0001-7358-368X
Brian D QuinlanDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.
Haiyong PengDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.ORCID 0000-0003-0312-1337
Guanqun LiuFlorida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, United States of America.ORCID 0000-0003-2520-7625
Yan GuoDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.
Shoujiao PengDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.
Lizhou ZhangDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.
Meredith E Davis-GardnerDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.ORCID 0000-0002-6133-3613
Matthew R GardnerDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.
Gogce CrynenBioinformatics and Statistics Core, The Scripps Research Institute, Jupiter, FL, United States of America.ORCID 0000-0001-6066-9900
Lindsey B DeVauxDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.ORCID 0000-0002-9064-5325
Zhi Xiang VooDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.
Charles C BaileyEmmune, Inc., Juno Beach, FL, United States of America.ORCID 0000-0003-0200-3523
Michael D AlpertEmmune, Inc., Juno Beach, FL, United States of America.ORCID 0000-0002-4056-9707
Christoph RaderDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.ORCID 0000-0001-9955-3454
Michaela U GackFlorida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, United States of America.ORCID 0000-0002-2163-2598
Hyeryun ChoeDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.
Michael FarzanDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States of America.ORCID 0000-0002-2990-5319
Scripps Research Institute · USCleveland Clinic Florida · USEmmune (United States) · US

Funding

Optimizing eCD4-Ig for eradication and a functional cureR01AI129868 · NIAID · UNIVERSITY OF FLORIDA · PI FARZAN, MICHAEL R. · 2017 to 2021
$5.2M
NIAID NIH HHS R01 AI129868
6 · The paper itself

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme 2 (ACE2). ACE2 is also the viral receptor of SARS-CoV (SARS-CoV-1), a related coronavirus that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus) are presumed to be the original reservoir of both viruses, and a SARS-like coronavirus, RaTG13, closely related to SARS-CoV-2, has been identified in one horseshoe-bat species. Here we characterize the ability of the S-protein receptor-binding domains (RBDs) of SARS-CoV-1, SARS-CoV-2, pangolin coronavirus (PgCoV), RaTG13, and LyRa11, a bat virus similar to SARS-CoV-1, to bind a range of ACE2 orthologs. We observed that the PgCoV RBD bound human ACE2 at least as efficiently as the SARS-CoV-2 RBD, and that both RBDs bound pangolin ACE2 efficiently. We also observed a high level of variability in binding to closely related horseshoe-bat ACE2 orthologs consistent with the heterogeneity of their RBD-binding regions. However five consensus horseshoe-bat ACE2 residues enhanced ACE2 binding to the SARS-CoV-2 RBD and neutralization of SARS-CoV-2 pseudoviruses by an enzymatically inactive immunoadhesin form of human ACE2 (hACE2-NN-Fc). Two of these mutations impaired neutralization of SARS-CoV-1 pseudoviruses. An hACE2-NN-Fc variant bearing all five mutations neutralized both SARS-CoV-2 pseudovirus and infectious virus more efficiently than wild-type hACE2-NN-Fc. These data suggest that SARS-CoV-1 and -2 originate from distinct bat species, and identify a more potently neutralizing form of soluble ACE2.

Indexed as

Angiotensin-Converting Enzyme 2AnimalsChiropteraCOVID-19Host SpecificityHumansModels, MolecularMutationProtein BindingReceptors, VirusSARS-CoV-2Spike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Receptors, VirusSpike Glycoprotein, Coronavirus

Identifiers

PMID33836016
PMCPMC8059821
OpenAlexW3146442259

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.