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

The host-virus evolutionary arms race over time leads to natural selection that alters both the host and the viral proteins allowing both to increase their fitness (Daugherty and Malik, 2012) . In this context multiple studies have analyzed and identified the origin, evolution and successful adaption of the SARS coronaviruses as human pathogens (Andersen et al., 2020; Guo et al., 2020) . Viral genome sequencing and analysis has identified bats as the most likely natural host of origin for both SARS-. CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.07.024752 doi: bioRxiv preprint CoV and the recent SARS-CoV-2 . In particular, several studies have focused on the viral S-protein RBD that interacts with its host ACE2 receptor and identified key changes between the bat CoVs and other suspected intermediary host CoVs found in the civet and pangolin (Andersen et al., 2020; Chen et al., 2020; Shang et al., 2020; Walls et al., 2020; Wrapp et al., 2020; Yan et al., 2020) . These studies have identified S-protein changes that have rendered the human cells permissive to the SARS-CoV and SARS-CoV-2 infection Shang et al., 2020; Walls et al., 2020; Wrapp et al., 2020; Yan et al., 2020) .