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Title: Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2
Authors: Suryamohan, Kushal
Diwanji, Devan
Stawiski, Eric W.
Gupta, Ravi
Miersch, Shane
Liu, Jiang
Chen, Chao
Jiang, Ying-Ping
Fellouse, Frederic A.
Sathirapongsasuti, J. Fah
Albers, Patrick K.
Deepak, Tanneeru
Saberianfar, Reza
Ratan, Aakrosh
Washburn, Gavin
Mis, Monika
Santhosh, Devi
Somasekar, Sneha
Hiranjith, G. H.
Vargas, Derek
Mohan, Sangeetha
Phalke, Sameer
Kuriakose, Boney
Antony, Aju
Ustav, Mart
Schuster, Stephan Christoph
Sidhu, Sachdev
Junutula, Jagath R.
Jura, Natalia
Seshagiri, Somasekar
Keywords: Engineering::Environmental engineering
Issue Date: 2021
Source: Suryamohan, K., Diwanji, D., Stawiski, E. W., Gupta, R., Miersch, S., Liu, J., Chen, C., Jiang, Y., Fellouse, F. A., Sathirapongsasuti, J. F., Albers, P. K., Deepak, T., Saberianfar, R., Ratan, A., Washburn, G., Mis, M., Santhosh, D., Somasekar, S., Hiranjith, G. H., ...Seshagiri, S. (2021). Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2. Communications Biology, 4(1), 475-.
Journal: Communications Biology 
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.
ISSN: 2399-3642
DOI: 10.1038/s42003-021-02030-3
Rights: © 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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