Evidence map›Paper›PMID 34109257›Full record

ArticleOpen forum infectious diseases2021

In Silico Evaluation of Cyclophilin Inhibitors as Potential Treatment for SARS-CoV-2.

Kyle Laurie, David Holcomb, Jacob Kames, Anton A Komar, Michael DiCuccio, Juan C Ibla, Chava Kimchi-Sarfaty

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Open forum infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Cyclophilin A-mediated mitigation of coronavirus SARS-CoV-2.Bioengineering & translational medicine · 2023
    Article
  5. Article
  6. The Cyclophilin-Dependent Calcineurin Inhibitor Voclosporin Inhibits SARS-CoV-2 Replication in Cell Culture.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Article
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

7 authors.

Kyle LaurieCenter for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, Maryland, USA.
David HolcombCenter for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, Maryland, USA.
Jacob KamesCenter for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, Maryland, USA.
Anton A KomarCenter for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, Ohio, USA.
Michael DiCuccioNational Center of Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
Juan C IblaDivision of Cardiac Anesthesia, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Chava Kimchi-SarfatyCenter for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, Maryland, USA.

Funding

Safer and more effective FIX therapeutics: impact of codon optimizationR01HL151392 · NHLBI · CLEVELAND STATE UNIVERSITY · PI KOMAR, ANTON A. · 2020 to 2023
$1.5M
NHLBI NIH HHS R01 HL151392
6 · The paper itself

Abstract

backgroundThe advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked researchers to propose multiple antiviral strategies to improve patients' outcomes. Studies provide evidence that cyclosporine A (CsA) decreases SARS-CoV-2 replication in vitro and decreases mortality rates of coronavirus disease 2019 (COVID-19) patients. CsA binds cyclophilins, which isomerize prolines, affecting viral protein activity.

methodsWe investigated the proline composition from various coronavirus proteomes to identify proteins that may critically rely on cyclophilin's peptidyl-proline isomerase activity and found that the nucleocapsid (N) protein significantly depends on cyclophilin A (CyPA). We modeled CyPA and N protein interactions to demonstrate the N protein as a potential indirect therapeutic target of CsA, which we propose may impede coronavirus replication by obstructing nucleocapsid folding.

resultsFinally, we analyzed the literature and protein-protein interactions, finding evidence that, by inhibiting CyPA, CsA may impact coagulation proteins and hemostasis.

conclusionsDespite CsA's promising antiviral characteristics, the interactions between cyclophilins and coagulation factors emphasize risk stratification for COVID patients with thrombosis dispositions.

Indexed as

ADAMTS13antiviralcoagulopathyCOVID-19cyclophilincyclosporine A

Identifiers

PMID34109257
PMCPMC8083350

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.