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

Communications Biology
K. SuryamohanSomasekar Seshagiri

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. Consisten...Continue Reading

References

May 16, 2003·The New England Journal of Medicine·Kathryn V Holmes
Dec 13, 2003·The Journal of Biological Chemistry·Swee Kee WongMichael Farzan
Mar 26, 2005·The EMBO Journal·Wenhui LiMichael Farzan
Aug 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Oct 19, 2007·Nature·UNKNOWN International HapMap ConsortiumJohn Stewart
Mar 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sandrine BelouzardGary R Whittaker
Feb 1, 2012·The Journal of Biological Chemistry·Kailang WuFang Li
Apr 18, 2012·International Journal of Epidemiology·Abigail FraserDebbie A Lawlor
Oct 19, 2012·The New England Journal of Medicine·Ali M ZakiRon A M Fouchier
Nov 14, 2012·Annual Review of Genetics·Matthew D Daugherty, Harmit S Malik
Jul 19, 2013·Genome Research·Gaurav BhatiaAlkes L Price
Mar 1, 1951·Annals of Eugenics·S WRIGHT
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Sep 1, 2016·Annual Review of Virology·Fang Li
Jun 23, 2018·The European Respiratory Journal·Christophe GuignabertMarc Lombès
Jun 27, 2019·Human Genome Variation·Shu TadakaKengo Kinoshita
Dec 6, 2019·Nature·UNKNOWN GenomeAsia100K Consortium
Jan 18, 2020·PLoS Biology·Patrick K Albers, Gil McVean
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Feb 23, 2020·Biochemical and Biophysical Research Communications·Yun ChenZhizhuang Joe Zhao
Mar 5, 2020·Nature Reviews. Drug Discovery·Guangdi Li, Erik De Clercq
Mar 20, 2020·Cell & Bioscience·Kit-San YuenDong-Yan Jin
Mar 21, 2020·Science·Anders BergströmChris Tyler-Smith
Apr 1, 2020·Nature·Jian ShangFang Li
Apr 7, 2020·Journal of Medical Virology·Mushtaq HussainBasma Aziz

❮ Previous
Next ❯

Citations

Jun 21, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·L Ponoop Prasad PatroThenmalarchelvi Rathinavelan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.