Author: 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 Jr, Mart; Schuster, Stephan C.; Sidhu, Sachdev; Junutula, Jagath R.; Jura, Natalia; Seshagiri, Somasekar
Title: Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2 Cord-id: nksgulf7 Document date: 2021_4_12
ID: nksgulf7
Snippet: 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 da
Document: 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.
Search related documents:
Co phrase search for related documents- accession number and low number: 1
- acute sars cov respiratory syndrome coronavirus and adaptive innate: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72
- acute sars cov respiratory syndrome coronavirus and adaptive innate immunity: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31
- acute sars cov respiratory syndrome coronavirus and adaptive innate immunity role: 1, 2, 3, 4
- acute sars cov respiratory syndrome coronavirus and additional factor: 1, 2, 3, 4, 5, 6, 7
- acute sars cov respiratory syndrome coronavirus and loop conformation: 1, 2, 3
- acute sars cov respiratory syndrome coronavirus and low number: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33
- acute sars cov respiratory syndrome coronavirus and luciferase assay system: 1
- acute sars cov respiratory syndrome coronavirus and luciferase signal: 1
- adaptive innate and low number: 1, 2, 3, 4
- adaptive innate immunity and low number: 1, 2
Co phrase search for related documents, hyperlinks ordered by date