Evidence map›Paper›PMID 32452762›Full record

ArticleeLife2020

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

Praveen Anand, Arjun Puranik, Murali Aravamudan, A J Venkatakrishnan, Venky Soundararajan

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
3.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 159 citations in OpenAlex.

  1. Green Synthesis Characterization and Evaluation ofMolecules (Basel, Switzerland) · 2026
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  8. Epithelial NaComprehensive Physiology · 2024
    Review
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  10. Article
  11. Review
  12. Acute abdomen following COVID-19 vaccination: a systematic review.Clinical and experimental vaccine research · 2024
    Article
  13. Article
  14. Article
  15. Review
  16. Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Review
  17. Is intestinal transport dysfunctional in COVID-19-related diarrhea?American journal of physiology. Gastrointestinal and liver physiology · 2023
    Article
  18. The Epithelial Sodium Channel-An Underestimated Drug Target.International journal of molecular sciences · 2023
    Review
  19. Review
  20. Article

24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Praveen Anandnference Labs, Bengaluru, India.ORCID 0000-0002-2478-7042
Arjun Puraniknference, Inc, Cambridge, United States.
Murali Aravamudannference, Inc, Cambridge, United States.
A J Venkatakrishnannference, Inc, Cambridge, United States.ORCID 0000-0003-2819-3214
Venky Soundararajannference, Inc, Cambridge, United States.ORCID 0000-0001-7434-9211
Nference (United States) · USNference (India) · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Molecular MimicryAngiotensin-Converting Enzyme 2BetacoronavirusCoronavirus InfectionsCOVID-19Epithelial Sodium ChannelsHost-Pathogen InteractionsHumansPandemicsPeptide HydrolasesPeptidyl-Dipeptidase APneumonia, ViralProteolysisSARS-CoV-2Substrate SpecificityViral Envelope ProteinsACE2 protein, humanAce2 protein, mouseAngiotensin-Converting Enzyme 2Epithelial Sodium ChannelsPeptide HydrolasesPeptidyl-Dipeptidase ASCNN1A protein, humanS envelope protein, hepatitis B virusViral Envelope ProteinsViral Proteinsacute respiratory distress syndromecomputational biologycoronavirusCOVID-19ENaChumanhuman biologymedicinemolecular mimicrymouseSARS-CoV-2systems biologyvirus

Identifiers

PMID32452762
PMCPMC7343387
OpenAlexW3030602524

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.