Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility

Eric W. Stawiski, Devan Diwanji, Kushal Suryamohan, Ravi Gupta, Frederic A. Fellouse, J. Fah Sathirapongsasuti, Jiang Liu, Ying-Ping Jiang, Aakrosh Ratan, Monika Mis, Devi Santhosh, Sneha Somasekar, Sangeetha Mohan, Sameer Phalke, Boney Kuriakose, Aju Antony, Jagath R. Junutula, Stephan C. Schuster, Natalia Jura, Somasekar Seshagiri
doi: https://doi.org/10.1101/2020.04.07.024752
Eric W. Stawiski
1Research and Development Department, MedGenome Inc., Foster City, CA 94404, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Devan Diwanji
2Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158, USA
3Department of Cellular and Molecular Pharmacology University of California San Francisco, San Francisco, CA 94158, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kushal Suryamohan
1Research and Development Department, MedGenome Inc., Foster City, CA 94404, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ravi Gupta
4MedGenome Labs Ltd., 3rd Floor, Narayana Nethralaya Building, Narayana Health City, #258/A, Bommasandra, Hosur Road, Bangalore, Karnataka 560099, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frederic A. Fellouse
5ModMab Therapeutics, Accelerator for Donnelly Collaboration, University of Toronto, Toronto, Ontario M5S 1A8, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Fah Sathirapongsasuti
1Research and Development Department, MedGenome Inc., Foster City, CA 94404, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jiang Liu
6ModMab Therapeutics, 348 Hatch Drive, Foster City, CA 94404, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ying-Ping Jiang
6ModMab Therapeutics, 348 Hatch Drive, Foster City, CA 94404, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aakrosh Ratan
7Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
8GenomeAsia100K Consortium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Monika Mis
1Research and Development Department, MedGenome Inc., Foster City, CA 94404, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Devi Santhosh
1Research and Development Department, MedGenome Inc., Foster City, CA 94404, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sneha Somasekar
9Midwestern University, Glendale, AZ 85308
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sangeetha Mohan
10Department of Molecular Biology, SciGenom Labs Pvt Ltd, Kerala 682037, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sameer Phalke
10Department of Molecular Biology, SciGenom Labs Pvt Ltd, Kerala 682037, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Boney Kuriakose
11AgriGenome Labs Private Ltd, Kochi, Kerala 682030, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aju Antony
10Department of Molecular Biology, SciGenom Labs Pvt Ltd, Kerala 682037, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jagath R. Junutula
6ModMab Therapeutics, 348 Hatch Drive, Foster City, CA 94404, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephan C. Schuster
8GenomeAsia100K Consortium
12Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Natalia Jura
2Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158, USA
3Department of Cellular and Molecular Pharmacology University of California San Francisco, San Francisco, CA 94158, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: natalia.Jura@ucsf.edu sekar@sgrf.org
Somasekar Seshagiri
6ModMab Therapeutics, 348 Hatch Drive, Foster City, CA 94404, USA
13SciGenom Research Foundation, 3rd Floor, Narayana Nethralaya Building, Narayana Health City, #258/A, Bommasandra, Hosur Road, Bangalore, Karnataka, 560099, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: natalia.Jura@ucsf.edu sekar@sgrf.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19) that has resulted in a global pandemic. It is a highly contagious positive strand RNA virus and its clinical presentation includes severe to critical respiratory disease that appears to be fatal in ∼3-5% of the cases. The viral spike (S) coat protein engages the human angiotensin-converting enzyme2 (ACE2) cell surface protein to invade the host cell. The SARS-CoV-2 S-protein has acquired mutations that increase its affinity to human ACE2 by ∼10-15-fold compared to SARS-CoV S-protein, making it highly infectious. In this study, we assessed if ACE2 polymorphisms might alter host susceptibility to SARS-CoV-2 by affecting the ACE2 S-protein interaction. Our comprehensive analysis of several large genomic datasets that included over 290,000 samples representing >400 population groups identified multiple ACE2 protein-altering variants, some of which mapped to the S-protein-interacting ACE2 surface. Using recently reported structural data and a recent S-protein-interacting synthetic mutant map of ACE2, we have identified natural ACE2 variants that are predicted to alter the virus-host interaction and thereby potentially alter host susceptibility. In particular, human ACE2 variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R are predicted to increase susceptibility. The T92I variant, part of a consensus NxS/T N-glycosylation motif, confirmed the role of N90 glycosylation in immunity from non-human CoVs. Other ACE2 variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y are putative protective variants predicted to show decreased binding to SARS-CoV-2 S-protein. Overall, ACE2 variants are rare, consistent with the lack of selection pressure given the recent history of SARS-CoV epidemics, however, are likely to play an important role in altering susceptibility to CoVs.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted April 10, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility
Eric W. Stawiski, Devan Diwanji, Kushal Suryamohan, Ravi Gupta, Frederic A. Fellouse, J. Fah Sathirapongsasuti, Jiang Liu, Ying-Ping Jiang, Aakrosh Ratan, Monika Mis, Devi Santhosh, Sneha Somasekar, Sangeetha Mohan, Sameer Phalke, Boney Kuriakose, Aju Antony, Jagath R. Junutula, Stephan C. Schuster, Natalia Jura, Somasekar Seshagiri
bioRxiv 2020.04.07.024752; doi: https://doi.org/10.1101/2020.04.07.024752
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility
Eric W. Stawiski, Devan Diwanji, Kushal Suryamohan, Ravi Gupta, Frederic A. Fellouse, J. Fah Sathirapongsasuti, Jiang Liu, Ying-Ping Jiang, Aakrosh Ratan, Monika Mis, Devi Santhosh, Sneha Somasekar, Sangeetha Mohan, Sameer Phalke, Boney Kuriakose, Aju Antony, Jagath R. Junutula, Stephan C. Schuster, Natalia Jura, Somasekar Seshagiri
bioRxiv 2020.04.07.024752; doi: https://doi.org/10.1101/2020.04.07.024752

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3602)
  • Biochemistry (7569)
  • Bioengineering (5524)
  • Bioinformatics (20792)
  • Biophysics (10328)
  • Cancer Biology (7981)
  • Cell Biology (11638)
  • Clinical Trials (138)
  • Developmental Biology (6603)
  • Ecology (10202)
  • Epidemiology (2065)
  • Evolutionary Biology (13617)
  • Genetics (9541)
  • Genomics (12847)
  • Immunology (7921)
  • Microbiology (19541)
  • Molecular Biology (7658)
  • Neuroscience (42096)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2202)
  • Physiology (3267)
  • Plant Biology (7041)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1951)
  • Systems Biology (5426)
  • Zoology (1117)