Evidence map›Paper›PMID 33811811›Full record

ArticleCell reports2021

Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2.

Mark Dittmar, Jae Seung Lee, Kanupriya Whig, Elisha Segrist, Minghua Li, Brinda Kamalia, Lauren Castellana, Kasirajan Ayyanathan, Fabian L Cardenas-Diaz, Edward E Morrisey and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed, 1 pooled it
17.9field-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

175 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.

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115 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

17 authors at 3 institutions in 2 countries.

Mark DittmarDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jae Seung LeeDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kanupriya WhigDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA.
Elisha SegristDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Minghua LiDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Brinda KamaliaDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA.
Lauren CastellanaDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kasirajan AyyanathanDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Fabian L Cardenas-DiazDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Edward E MorriseyDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rachel TruittDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Wenli YangDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kellie JuradoDepartment of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.
Kirandeep SambyMedicines for Malaria Venture, Geneva, Switzerland.
Holly RamageDepartment of Microbiology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: holly.ramage@jefferson.edu.
David C SchultzDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: dschultz@upenn.edu.
Sara CherryDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: cherrys@pennmedicine.upenn.edu.
University of Pennsylvania · USMedicines for Malaria Venture · CHThomas Jefferson University · US

Funding

Training in Emerging Infectious DiseasesT32AI055400 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHERRY, SARA, HENSLEY, SCOTT ERIC · 2003 to 2022
$4.4M
The role of pattern recognition and autophagy in innate anti-bunyaviral immunityR01AI150246 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHERRY, SARA · 2019 to 2023
$3.5M
Bidirectional signaling in T cell differentiationR01AI150241 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Hongbo Chi · 2019 to 2026
$3.3M
Defining the functional interface between the ER and flavivirusesR01AI140539 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHERRY, SARA, DIAMOND, MICHAEL S · 2018 to 2022
$3.0M
Defining the role of microbiota-derived cyclic dinucleotides in priming antiviral immune defenses.R01AI152362 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHERRY, SARA · 2020 to 2024
$2.0M
NIAID NIH HHS R01 AI140539NIAID NIH HHS R01 AI150241NIAID NIH HHS R01 AI150246NIAID NIH HHS R01 AI152362NIAID NIH HHS T32 AI055400
6 · The paper itself

Abstract

There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of ∼3,000 drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation.

Indexed as

COVID-19 Drug TreatmentDrug RepositioningAnimalsChlorocebus aethiopsCOVID-19CyclosporineEpithelial CellsHumansLungSARS-CoV-2Serine EndopeptidasesUnited StatesUnited States Food and Drug AdministrationVero CellsCyclosporineSerine EndopeptidasesTMPRSS2 protein, humanantiviralcoronaviruscyclophilincyclosporindrugsentryHTSSARS2screeningTMPRSS2

Identifiers

PMID33811811
PMCPMC7985926
OpenAlexW3137359073

What OpenQuestion holds

Textmetadata
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.