Evidence map›Paper›PMID 33846513›Full record

ArticleCommunications biology2021

Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2.

Kushal Suryamohan, Devan Diwanji, Eric W Stawiski, Ravi Gupta, Shane Miersch, Jiang Liu, Chao Chen, Ying-Ping Jiang, Frederic A Fellouse, J Fah Sathirapongsasuti and 20 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed, 3 pooled it
11.2field-weighted citation impact, top 1% 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

175 citing papers in PubMed, 3 syntheses or guidelines pooled it, 231 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

115 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

30 authors at 9 institutions in 5 countries.

Kushal Suryamohan *Research and Development Department, MedGenome Inc, Foster City, CA, USA.ORCID 0000-0002-6614-7182
Devan Diwanji *Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
Eric W Stawiski *Research and Development Department, MedGenome Inc, Foster City, CA, USA.
Ravi GuptaMedGenome Labs Ltd., Bangalore, Karnataka, India.
Shane MierschDepartment of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Jiang LiuModMab Therapeutics, Foster City, CA, USA.
Chao ChenDepartment of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.ORCID 0000-0003-1028-3182
Ying-Ping JiangModMab Therapeutics, Foster City, CA, USA.
Frederic A FellouseModMab Therapeutics, Accelerator for Donnelly Collaboration, University of Toronto, Toronto, ON, Canada.
J Fah SathirapongsasutiResearch and Development Department, MedGenome Inc, Foster City, CA, USA.
Patrick K AlbersWellcome Sanger Institute, Cambridge, UK.ORCID 0000-0003-2770-3729
Tanneeru DeepakMedGenome Labs Ltd., Bangalore, Karnataka, India.
Reza SaberianfarModMab Therapeutics, Accelerator for Donnelly Collaboration, University of Toronto, Toronto, ON, Canada.
Aakrosh RatanCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Gavin WashburnResearch and Development Department, MedGenome Inc, Foster City, CA, USA.
Monika MisResearch and Development Department, MedGenome Inc, Foster City, CA, USA.
Devi SanthoshModMab Therapeutics, Foster City, CA, USA.
Sneha SomasekarMidwestern University, Glendale, AZ, USA.
G H HiranjithResearch and Development Department, MedGenome Inc, Foster City, CA, USA.
Derek VargasResearch and Development Department, MedGenome Inc, Foster City, CA, USA.
Sangeetha MohanDepartment of Molecular Biology, SciGenom Labs Pvt Ltd, Kochi, Kerala, India.
Sameer PhalkeDepartment of Molecular Biology, SciGenom Labs Pvt Ltd, Kochi, Kerala, India.
Boney KuriakoseAgriGenome Labs Private Ltd, Kochi, Kerala, India.
Aju AntonyDepartment of Molecular Biology, SciGenom Labs Pvt Ltd, Kochi, Kerala, India.
Mart UstavDepartment of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Stephan C SchusterSingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.
Sachdev SidhuDepartment of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-7755-5918
Jagath R JunutulaModMab Therapeutics, Foster City, CA, USA.
Natalia JuraCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA. natalia.jura@ucsf.edu.ORCID 0000-0001-5129-641X
Somasekar SeshagiriModMab Therapeutics, Foster City, CA, USA. sekar@sgrf.org.ORCID 0000-0003-4272-6443
Depomed (United States) · USSciGenom Labs (India) · INUniversity of Toronto · CAUniversity of California, San Francisco · USMidwestern University · USNanyang Technological University · SGSciGenom Research Foundation · INUniversity of Virginia · USWellcome Sanger Institute · GB

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Investigating oncogenic mutations and regulatory mechanisms of HER2 by electron microscopyF30CA247147 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DIWANJI, DEVAN · 2020 to 2023
$163k
Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_19009NCI NIH HHS F30 CA247147NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

COVID-19 is a respiratory illness caused by a novel coronavirus called SARS-CoV-2. The viral spike (S) protein engages the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells with ~10-15-fold higher affinity compared to SARS-CoV S-protein, making it highly infectious. Here, we assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction. We analyzed over 290,000 samples representing >400 population groups from public genomic datasets and identified multiple ACE2 protein-altering variants. Using reported structural data, we identified natural ACE2 variants that could potentially affect virus-host interaction and thereby alter host susceptibility. These include variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R that were predicted to increase susceptibility, while variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y were predicted to be protective variants that show decreased binding to S-protein. Using biochemical assays, we confirmed that K31R and E37K had decreased affinity, and K26R and T92I variants showed increased affinity for S-protein when compared to wildtype ACE2. Consistent with this, soluble ACE2 K26R and T92I were more effective in blocking entry of S-protein pseudotyped virus suggesting that ACE2 variants can modulate susceptibility to SARS-CoV-2.

Indexed as

Polymorphism, GeneticAmino Acid SequenceAngiotensin-Converting Enzyme 2COVID-19Genetic Predisposition to DiseaseHost-Pathogen InteractionsHumansModels, MolecularMutation, MissenseProtein BindingProtein DomainsReceptors, VirusSARS-CoV-2Sequence Homology, Amino AcidSpike Glycoprotein, CoronavirusVirus InternalizationAngiotensin-Converting Enzyme 2Receptors, VirusSpike Glycoprotein, Coronavirusspike glycoprotein, SARS-CoV

Identifiers

PMID33846513
PMCPMC8041869
OpenAlexW3156747712

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.