Duke Health Joins with nference to Advance Medical Research and Patient Care
< Back to All Publications
SARS-CoV-2 strategically mimics proteolytic activation of human ENaC
May 26 2020
Molecular mimicry of host proteins is an evolutionary strategy adopted by viruses to evade immune surveillance and exploit host cell systems. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site (RRARSVAS), absent in any previous coronavirus sequenced, that results in mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic truncation at this ENaC-α cleavage site causes aldosterone dysregulation in patients, highlighting the functional importance of the mimicked SARS-CoV-2 peptide. Single cell RNA-seq from 65 studies shows significant overlap between the expression of ENaC-α and ACE2, the putative receptor for the virus, in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular fingerprint with amino acid cleavage signatures of 178 human proteases shows the potential for tissue-specific proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. We extrapolate that the evolution of SARS-CoV-2 into a global coronavirus pandemic may be in part due to its targeted mimicry of human ENaC and hijack of the associated host proteolytic network.
Praveen Anand, Arjun Puranik, Murali Aravamudan, AJ Venkatakrishnan, Venky Soundararajan
nference Cambridge, United States nference Labs Bangalore, India
AJ Venkatakrishnan (email@example.com), Venky Soundararajan (firstname.lastname@example.org)
Let’s talk about how we can work together.
Fill out the form and we’ll get right back to you.