SARS-CoV-2 strategically mimics proteolytic activation of human ENaC

Praveen AnandVenky Soundararajan


Molecular mimicry is an evolutionary strategy adopted by viruses to exploit the host cellular machinery. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in the striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC. Single cell RNA-seq from 66 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular characterization with cleavage signatures of 178 proteases highlights proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. Evolution of SARS-CoV-2 into a global pandemic may be driven in part by its targeted mimicry of ENaC-α, a protein critical for the homeostasis of airway surface liquid, whose misregulation is associated with respiratory conditions.


Mar 10, 2004·The Journal of Biological Chemistry·Rebecca P HugheyThomas R Kleyman
Oct 7, 2004·The Journal of Biological Chemistry·Rebecca P HugheyThomas R Kleyman
Oct 22, 2008·Annual Review of Physiology·Bernard C Rossier, M Jackson Stutts
Nov 5, 2008·Nucleic Acids Research·Mauricio Carrillo-TrippVijay S Reddy
Nov 5, 2008·The Journal of Biological Chemistry·Christopher J PasseroThomas R Kleyman
Mar 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sandrine BelouzardGary R Whittaker
Mar 30, 2010·Biochimica Et Biophysica Acta·Michael B Butterworth
Sep 3, 2010·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Murat Yurdakök
Jul 21, 2012·Viruses·Sandrine BelouzardGary R Whittaker
Feb 19, 2013·European Journal of Endocrinology·Maik WelzelFelix G Riepe
Sep 27, 2018·ELife·Sigrid NorengIsabelle Baconguis
Jan 10, 2017·Global Challenges·Stefan Elbe, Gemma Buckland-Merrett
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Mar 21, 2020·Current Biology : CB·Tao ZhangZhigang Zhang

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