Evidence map›Paper›PMID 37243214›Full record

ArticleViruses2023

DHFR Inhibitors Display a Pleiotropic Anti-Viral Activity against SARS-CoV-2: Insights into the Mechanisms of Action.

Daniela Iaconis, Francesca Caccuri, Candida Manelfi, Carmine Talarico, Antonella Bugatti, Federica Filippini, Alberto Zani, Rubina Novelli, Maria Kuzikov, Bernhard Ellinger and 8 more

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 8 citations in OpenAlex.

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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

18 authors at 5 institutions in 2 countries.

Daniela IaconisEXSCALATE, Dompé Farmaceutici SpA, Via Tommaso De Amicis, 95, 80131 Napoli, Italy.ORCID 0000-0002-1052-6634
Francesca CaccuriSection of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.ORCID 0000-0002-1923-9033
Candida ManelfiEXSCALATE, Dompé Farmaceutici SpA, Via Tommaso De Amicis, 95, 80131 Napoli, Italy.
Carmine TalaricoEXSCALATE, Dompé Farmaceutici SpA, Via Tommaso De Amicis, 95, 80131 Napoli, Italy.ORCID 0000-0003-4789-0955
Antonella BugattiSection of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.ORCID 0000-0001-5450-5774
Federica FilippiniSection of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Alberto ZaniSection of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.ORCID 0000-0001-9066-7973
Rubina NovelliDompè Famaceutici SpA, Via Campo di Pile snc, 67100 L'Aquila, Italy.ORCID 0000-0002-7990-7507
Maria KuzikovFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany.ORCID 0000-0001-8771-1865
Bernhard EllingerFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany.
Philip GribbonFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany.
Kristoffer RieckenResearch Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.ORCID 0000-0001-9050-6766
Francesca EspositoDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria SS554, 09042 Monserrato (CA), Italy.ORCID 0000-0001-9725-7977
Angela CoronaDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria SS554, 09042 Monserrato (CA), Italy.ORCID 0000-0002-6630-8636
Enzo TramontanoDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria SS554, 09042 Monserrato (CA), Italy.ORCID 0000-0002-4849-0980
Andrea Rosario BeccariEXSCALATE, Dompé Farmaceutici SpA, Via Tommaso De Amicis, 95, 80131 Napoli, Italy.ORCID 0000-0001-6830-2695
Arnaldo CarusoSection of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Marcello AllegrettiDompè Famaceutici SpA, Via Campo di Pile snc, 67100 L'Aquila, Italy.ORCID 0000-0002-0617-0233
Dompé (Italy) · ITUniversity of Brescia · ITMerck (Germany) · DEUniversity of Cagliari · ITUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During the COVID-19 pandemic, drug repurposing represented an effective strategy to obtain quick answers to medical emergencies. Based on previous data on methotrexate (MTX), we evaluated the anti-viral activity of several DHFR inhibitors in two cell lines. We observed that this class of compounds showed a significant influence on the virus-induced cytopathic effect (CPE) partly attributed to the intrinsic anti-metabolic activity of these drugs, but also to a specific anti-viral function. To elucidate the molecular mechanisms, we took advantage of our EXSCALATE platform for in-silico molecular modelling and further validated the influence of these inhibitors on nsp13 and viral entry. Interestingly, pralatrexate and trimetrexate showed superior effects in counteracting the viral infection compared to other DHFR inhibitors. Our results indicate that their higher activity is due to their polypharmacological and pleiotropic profile. These compounds can thus potentially give a clinical advantage in the management of SARS-CoV-2 infection in patients already treated with this class of drugs.

Indexed as

COVID-19SARS-CoV-2Antiviral AgentsDrug RepositioningHumansMolecular Docking SimulationPandemicsAntiviral Agentsanti-viral activityCOVID-19drug repurposingEXSCALATEmethotrexatemolecular dockingnsp13SARS-CoV-2viral entryvirtual screening

Identifiers

PMID37243214
PMCPMC10221469
OpenAlexW4378516370

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.