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.
Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites.
ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1.
The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database
Peripheral localization of the epithelial sodium channel in the apical membrane of bronchial epithelial cells
The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade
Knowledge synthesis of 100 million biomedical documents augments the deep expression profiling of coronavirus receptors
Augmented Curation of Unstructured Clinical Notes from a Massive EHR System Reveals Specific Phenotypic Signature of Impending COVID-19 Diagnosis
Augmented curation of clinical notes from a massive EHR system reveals symptoms of impending COVID-19 diagnosis.
COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein
Inter-proteomic posttranslational modifications of the SARS-CoV-2 and the host proteins ‒ A new frontier.
Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies.
Osmotic Adaptation by Na+ -Dependent Transporters and ACE2: Correlation with Hemostatic Crisis in COVID-19
A Pathophysiological Model for COVID-19: Critical Importance of Transepithelial Sodium Transport upon Airway Infection.
Hypothetical dysfunction of the epithelial sodium channel may justify neurohumoral blockade in coronavirus disease 2019.
Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases.
Common low complexity regions for SARS-CoV-2 and human proteomes as potential multidirectional risk factor in vaccine development.
Neuropsychiatric Symptoms of COVID-19 Explained by SARS-CoV-2 Proteins' Mimicry of Human Protein Interactions.
Role of Serine Proteases and Host Cell Receptors Involved in Proteolytic Activation, Entry of SARS-CoV-2 and Its Current Therapeutic Options.
A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry.
COVID-19: the CaMKII-like system of S protein drives membrane fusion and induces syncytial multinucleated giant cells.
Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing.
Next-Generation Sequencing (NGS) in COVID-19: A Tool for SARS-CoV-2 Diagnosis, Monitoring New Strains and Phylodynamic Modeling in Molecular Epidemiology.
Shell disorder analysis suggests that pangolins offered a window for a silent spread of an attenuated SARS-CoV-2 precursor among humans
Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.