Author response: SARS-CoV-2 strategically mimics proteolytic activation of human ENaC

Puranik, Arjun; Aravamudan, Murali; Venkatakrishnan, AJ; Soundararajan, Venky

doi:10.7554/elife.58603.sa2

Cited by 2 publications

(3 citation statements)

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“…Using in silico analysis of repertoires on the human proteome, we are also able to identify candidate cross-reactive or novel autoantigen epitopes that may be important in disease pathogenesis. The polybasic cleavage site seen in SARS-CoV-2 is unique among coronaviruses and potentially enables it to increase its tissue tropism 33 . We demonstrate that the immune response at this site is predicted to be both significantly prominent and prevalent relative to a pre-pandemic cohort, as well as significantly stronger in severe and moderate versus mild disease.…”

Section: Discussionmentioning

confidence: 99%

“…Cleavage of spike protein at this site is required to enable viral membrane fusion 31,32 . It has been proposed that this novel sequence enables the virus to take advantage of host proteases, such as furin, that cleave proteins with this recognition sequence, thereby increasing the potential tropism of the virus relative to other coronaviruses 31,33 . We asked if this site elicited an immune response, and if so, was it seen differentially in subjects with different disease severity.…”

Section: Motifs and Epitopes Associated With Disease Severitymentioning

confidence: 99%

“…The novel eight amino acid furin cleavage site (RRAR|SVAS) in spike maps identically to a peptide sequence in one protein in the human proteome, the amiloride sensitive sodium channel ENaC-α protein 33 . This protein is expressed on the surface of multiple tissues implicated in COVID-19 pathology, and similar to spike, requires cleavage for activation.…”

Section: Motifs and Epitopes Associated With Disease Severitymentioning

confidence: 99%

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High-resolution mapping and characterization of epitopes in COVID-19 patients

Haynes

Kamath

Bozekowski

et al. 2020

Preprint

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Fine scale delineation of epitopes recognized by the antibody response to SARS-CoV-2 infection will be critical to understanding disease heterogeneity and informing development of safe and effective vaccines and therapeutics. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify epitope binding specificities with single amino acid resolution. We applied SERA broadly, across human, viral and viral strain proteomes in multiple cohorts with a wide range of outcomes from SARS-CoV-2 infection. We identify dominant epitope motifs and profiles which effectively classify COVID-19, distinguish mild from severe disease, and relate to neutralization activity. We identify a repertoire of epitopes shared by SARS-CoV-2 and endemic human coronaviruses and determine that a region of amino acid sequence identity shared by the SARS-CoV-2 furin cleavage site and the host protein ENaC-alpha is a potential cross-reactive epitope. Finally, we observe decreased epitope signal for mutant strains which points to reduced antibody response to mutant SARS-CoV-2. Together, these findings indicate that SERA enables high resolution of antibody epitopes that can inform data-driven design and target selection for COVID-19 diagnostics, therapeutics and vaccines.

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Section: Discussionmentioning

confidence: 99%