Evidence map›Paper›PMID 35860224›Full record

ArticlebioRxiv : the preprint server for biology2022

In Vitro Evaluation and Mitigation of Niclosamide's Liabilities as a COVID-19 Treatment.

Jesse W Wotring, Sean M McCarty, Khadija Shafiq, Charles J Zhang, Theophilus Nguyen, Sophia R Meyer, Reid Fursmidt, Carmen Mirabelli, Martin C Clasby, Christiane E Wobus and 2 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Jesse W WotringDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Sean M McCartyDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Khadija ShafiqDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Charles J ZhangDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Theophilus NguyenDepartment of Internal Medicine, Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI, 48109, USA.
Sophia R MeyerDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Reid FursmidtDepartment of Internal Medicine, Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI, 48109, USA.
Carmen MirabelliDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
Martin C ClasbyDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Christiane E WobusDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
Matthew J O'MearaDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Jonathan Z SextonDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
University of Michigan · USMichigan Medicine · US

Funding

Michigan Institute for Clinical and Health Research (MICHR)UL1TR002240 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUMENG, JULIE C, MASHOUR, GEORGE ALEXANDER · 2017 to 2022
$54.9M
Small molecules for expansion of islet beta-cell mass in diabetesR01DK120623 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NEWGARD, CHRISTOPHER B, SEXTON, JONATHAN ZACHARY · 2019 to 2021
$2.0M
NCATS NIH HHS UL1 TR002240NIDDK NIH HHS R01 DK120623
6 · The paper itself

Abstract

Niclosamide, an FDA-approved oral anthelmintic drug, has broad biological activity including anticancer, antibacterial, and antiviral properties. Niclosamide has also been identified as a potent inhibitor of SARS-CoV-2 infection Importance: There is still an urgent need for effective anti-SARS-CoV-2 therapeutics due to waning vaccine efficacy, the emergence of variants of concern, and limited efficacy of existing antivirals. One potential therapeutic option is niclosamide, an FDA approved anthelmintic compound that has shown promising anti-SARS-CoV-2 activity in cell-based assays. Unfortunately, there are significant barriers for the clinical utility of niclosamide as a COVID-19 therapeutic. Our work emphasizes these limitations by showing that niclosamide has high cytotoxicity at antiviral concentrations, variable potency against variants of concern, and significant polypharmacology as a result of its activity as a nonspecific protonophore. Some of these clinical limitations can be mitigated, however, through structural modifications to the niclosamide scaffold, which we demonstrate through a preliminary structure activity relationship analysis. Overall, we show that niclosamide is not a suitable candidate for the treatment of COVID-19, but that structural analogs with improved drug properties may have higher clinical-translational potential.

Identifiers

PMID35860224
PMCPMC9298134
OpenAlexW4283455971

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.