Evidence map›Paper›PMID 34083527›Full record

ArticleNature communications2021

Drug repurposing screens identify chemical entities for the development of COVID-19 interventions.

Malina A Bakowski, Nathan Beutler, Karen C Wolff, Melanie G Kirkpatrick, Emily Chen, Tu-Trinh H Nguyen, Laura Riva, Namir Shaabani, Mara Parren, James Ricketts and 22 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
16.9field-weighted citation impact, top 1% 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

76 citing papers in PubMed, 127 citations in OpenAlex.

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16 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

32 authors at 2 institutions in 1 country.

Malina A Bakowski *Calibr, a division of The Scripps Research Institute, La Jolla, CA, USA. mbakowski@scripps.edu.ORCID 0000-0002-3337-6528
Nathan Beutler *Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-3240-9524
Karen C WolffCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Melanie G KirkpatrickCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Emily ChenCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Tu-Trinh H NguyenCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Laura RivaCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Namir ShaabaniDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-3548-5899
Mara ParrenDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
James RickettsDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-9057-5937
Anil K GuptaCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Kastin PanCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Peiting KuoCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-4407-4418
MacKenzie FullerDepartment of Cellular and Molecular Medicine, UC San Diego, La Jolla, CA, USA.
Elijah GarciaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
John R TeijaroDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Linlin YangDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Debashis SahooDepartment of Computer Science and Engineering, Jacobs School of Engineering, UC San Diego, La Jolla, CA, USA.ORCID 0000-0003-2329-8228
Victor ChiCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Edward HuangCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Natalia VargasCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-8537-6861
Amanda J RobertsAnimal Models Core Facility, The Scripps Research Institute, La Jolla, CA, USA.
Soumita DasHUMANOID CoRE, UC San Diego, La Jolla, CA, USA.ORCID 0000-0003-3895-3643
Pradipta GhoshDepartment of Cellular and Molecular Medicine, UC San Diego, La Jolla, CA, USA.ORCID 0000-0002-8917-3201
Ashley K WoodsCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Sean B JosephCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-2602-8517
Mitchell V HullCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Peter G SchultzCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-6711-9864
Arnab K ChatterjeeCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.
Case W McNamaraCalibr, a division of The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-5754-3407
Thomas F RogersDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. trogers@scripps.edu.ORCID 0000-0001-9756-327X
Scripps Research Institute · USUniversity of California San Diego · US

Funding

Macrophage Polarization in Response to Infections and InflammationR01AI155696 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA, SAHOO, DEBASHIS · 2020 to 2024
$4.9M
Modulation of Macrophage Polarization by Heterotrimeric G proteins: Implications of Gastrointestinal InflammationR01AI141630 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Pradipta Ghosh · 2019 to 2026
$3.2M
Innate responses following infection with enteric microbesR01DK107585 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAS, SOUMITA · 2016 to 2020
$2.2M
Summer Student Research on the Application of Boolean AnalysisR01GM138385 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SAHOO, DEBASHIS · 2020 to 2023
$2.0M
Precision therapeutics of inflammatory bowel disease guided by Boolean logicUG3TR003355 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAS, SOUMITA, GHOSH, PRADIPTA · 2020 to 2022
$937k
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NCATS NIH HHS UG3 TR003355NIAID NIH HHS R01 AI141630NIAID NIH HHS R01 AI155696NIDDK NIH HHS R01 DK107585NIGMS NIH HHS R01 GM138385NIH HHS S10 OD026929
6 · The paper itself

Abstract

The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.

Indexed as

COVID-19 Drug TreatmentPandemicsSARS-CoV-2AnimalsAntiviral AgentsCell LineCOVID-19CytidineDatabases, PharmaceuticalDrug DiscoveryDrug Evaluation, PreclinicalDrug RepositioningHeLa CellsHigh-Throughput Screening AssaysHumansHydroxylaminesAntiviral AgentsCytidineHydroxylaminesmolnupiravirNelfinavir

Identifiers

PMID34083527
PMCPMC8175350
OpenAlexW3165248908

What OpenQuestion holds

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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.