Evidence map›Paper›PMID 34407143›Full record

ArticlePloS one2021

Genomics-guided identification of potential modulators of SARS-CoV-2 entry proteases, TMPRSS2 and Cathepsins B/L.

Kartikay Prasad, Suliman Yousef AlOmar, Eman Abdullah Almuqri, Hassan Ahmed Rudayni, Vijay Kumar

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  3. Review
  4. Article
  5. Review
  6. SARS-CoV-2 Receptors and Their Involvement in Cell Infection.Biochemistry (Moscow) Supplement. Series A, Membrane and cell biology · 2023
    Article
  7. Review
  8. Article
  9. The immunology and immunotherapy for COVID-19.Expert reviews in molecular medicine · 2021
    Review
  10. Article
  11. Review
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 3 institutions in 2 countries.

Kartikay PrasadAmity Institute of Neuropsychology & Neurosciences (AINN), Amity University, Noida, UP, India.ORCID 0000-0002-8730-0967
Suliman Yousef AlOmarDepartment of College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Eman Abdullah AlmuqriDepartment of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
Hassan Ahmed RudayniBiology Department, College of Science, Imam Muhammad bin Saud Islamic University, Riyadh, Kingdom of Saudi Arabia.
Vijay KumarAmity Institute of Neuropsychology & Neurosciences (AINN), Amity University, Noida, UP, India.ORCID 0000-0002-3621-5025
Amity University · INImam Mohammad ibn Saud Islamic University · SAKing Saud University · SA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SARS-CoV-2 requires serine protease, transmembrane serine protease 2 (TMPRSS2), and cysteine proteases, cathepsins B, L (CTSB/L) for entry into host cells. These host proteases activate the spike protein and enable SARS-CoV-2 entry. We herein performed genomic-guided gene set enrichment analysis (GSEA) to identify upstream regulatory elements altering the expression of TMPRSS2 and CTSB/L. Further, medicinal compounds were identified based on their effects on gene expression signatures of the modulators of TMPRSS2 and CTSB/L genes. Using this strategy, estradiol and retinoic acid have been identified as putative SARS-CoV-2 alleviation agents. Next, we analyzed drug-gene and gene-gene interaction networks using 809 human targets of SARS-CoV-2 proteins. The network results indicate that estradiol interacts with 370 (45%) and retinoic acid interacts with 251 (31%) human proteins. Interestingly, a combination of estradiol and retinoic acid interacts with 461 (56%) of human proteins, indicating the therapeutic benefits of drug combination therapy. Finally, molecular docking analysis suggests that both the drugs bind to TMPRSS2 and CTSL with the nanomolar to low micromolar affinity. The results suggest that these drugs can simultaneously target both the entry pathways of SARS-CoV-2 and thus can be considered as a potential treatment option for COVID-19.

Indexed as

Cathepsin BCathepsin LDatabases, GeneticEstradiolGene Expression Regulation, EnzymologicGene Regulatory NetworksGenomicsHost-Pathogen InteractionsHumansModels, MolecularMolecular Docking SimulationProtein ConformationProtein Interaction MapsSARS-CoV-2Serine EndopeptidasesTretinoinCathepsin BCathepsin LCTSB protein, humanCTSL protein, humanEstradiolSerine EndopeptidasesTMPRSS2 protein, humanTretinoinViral Proteins

Identifiers

PMID34407143
PMCPMC8372896
OpenAlexW3114798091

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.