ArticleScience (New York, N.Y.)2021
Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2.
Open access · hybridAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed, 1 pooled it
15.3field-weighted citation impact, top 1% of its field
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Who cites it
140 citing papers in PubMed, 1 synthesis or guideline pooled it, 220 citations in OpenAlex.
- A systematic review on impact of SARS-CoV-2 infection.Microbiological research · 2023Pooled it
- The nematode Caenorhabditis elegans has a cationic amphiphilic drug (CAD) defense system.PLoS biology · 2026Article
- A Comparative Evaluation Framework Integrating Machine Learning and Deep Learning Models with ADME-Based Pharmacokinetic Assessment for HIV-Related Compounds.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Fusion Inhibition of Zika Virus Entry by a Teicoplanin Pseudoaglycone Derivative with Broad Antiviral Activity.Pharmaceutics · 2026Article
- Development and characterization of triazole-based WDR5 inhibitors for the treatment of glioblastoma.JCI insight · 2026Article
- Experimental and machine learning-based exploration of repurposed drugs reveals chemical features underlying phospholipidosis.Patterns (New York, N.Y.) · 2026Article
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- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- How Can Pharmacology Help Us Overcome the Challenges of Drug Repositioning as Antivirals to Treat Emerging Pathogens? The Example of Covid-19.Clinical and translational science · 2026Review
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- Drug-induced phospholipidosis as an artifact in antiviral drug repurposing.bioRxiv : the preprint server for biology · 2025Article
- Development of Lipopeptides as Orthoflavivirin Inhibitors with Low Micromolar Broad-Spectrum Antiorthoflaviviral Activity.Journal of medicinal chemistry · 2025Article
- Membrane Perturbations and Assay Interferences by Ivermectin Explain Its In Vitro SARS-CoV-2 Antiviral Activities and Lack of Translatability.Journal of medicinal chemistry · 2025Review
- Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.Acta pharmaceutica Sinica. B · 2025Article
- Disruption of Spike Priming in Virus Entry: Tetrandrine as a Pan-Coronavirus Inhibitor.MedComm · 2025Article
- A Structure-Based Computational Pipeline for Broad-Spectrum Antiviral Discovery.bioRxiv : the preprint server for biology · 2025Article
- Membrane-Targeting Antivirals.International journal of molecular sciences · 2025Review
- A cationic amphiphilic drug synergizes with strobilurin fungicides to control fungal-borne plant diseases.Cell chemical biology · 2025Article
- Guardians at the Gate: Optimization of Small Molecule Entry Inhibitors of Ebola and Marburg Viruses.Journal of medicinal chemistry · 2025Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 8 institutions in 4 countries.
Tia A Tummino *Department of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.ORCID 0000-0001-9155-820X
Veronica V Rezelj *Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.ORCID 0000-0003-1571-8325
Benoit Fischer *Novartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.ORCID 0000-0002-9911-1397
Audrey Fischer *Novartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.ORCID 0000-0001-9278-2393
Matthew J O'MearaDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3128-5331
Blandine MonelInstitut Pasteur, Virus and Immunity Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.ORCID 0000-0002-6096-873X
Thomas ValletInstitut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.ORCID 0000-0001-7775-7448
Kris M WhiteDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-0889-0506
Ziyang ZhangQuantitative Biosciences Institute (QBI), UCSF, San Francisco, CA, USA.ORCID 0000-0003-0541-7211
Assaf AlonDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8102-5290
Heiko SchadtNovartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.ORCID 0000-0002-1164-1140
Henry R O'DonnellDepartment of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.ORCID 0000-0001-6877-2048
Jiankun LyuDepartment of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.ORCID 0000-0002-0461-5454
Romel RosalesDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-5326-4753
Briana L McGovernDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Raveen RathnasingheDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-1260-2493
Sonia JangraDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Michael SchotsaertDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-3156-3132
Jean-René GalarneauNovartis Institutes for BioMedical Research, Preclinical Safety, Cambridge, MA, USA.
Nevan J KroganQuantitative Biosciences Institute (QBI), UCSF, San Francisco, CA, USA.ORCID 0000-0003-4902-337X
Laszlo UrbanNovartis Institutes for BioMedical Research, Preclinical Safety, Cambridge, MA, USA.ORCID 0000-0002-1275-0293
Kevan M ShokatQuantitative Biosciences Institute (QBI), UCSF, San Francisco, CA, USA.ORCID 0000-0001-8590-7741
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1467-1222
Adolfo García-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-6551-1827
Olivier SchwartzInstitut Pasteur, Virus and Immunity Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.ORCID 0000-0002-0729-1475
Francesca MorettiNovartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland. bshoichet@gmail.com francois.pognan@novartis.com marco.vignuzzi@pasteur.fr francesca.moretti@novartis.com.ORCID 0000-0003-0920-1063
Marco VignuzziInstitut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France. bshoichet@gmail.com francois.pognan@novartis.com marco.vignuzzi@pasteur.fr francesca.moretti@novartis.com.ORCID 0000-0002-4400-771X
Francois PognanNovartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland. bshoichet@gmail.com francois.pognan@novartis.com marco.vignuzzi@pasteur.fr francesca.moretti@novartis.com.ORCID 0000-0001-7033-2033
Brian K ShoichetDepartment of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA. bshoichet@gmail.com francois.pognan@novartis.com marco.vignuzzi@pasteur.fr francesca.moretti@novartis.com.ORCID 0000-0002-6098-7367
Icahn School of Medicine at Mount Sinai · USNovartis (Switzerland) · CHCentre National de la Recherche Scientifique · FRUniversity of California, San Francisco · USHarvard University · USHoward Hughes Medical Institute · USGladstone Institutes · USUniversity of Michigan · US
Funding
The role of Listeria cyclic-di-AMP during infection and immunityP01AI063302 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI PORTNOY, DANIEL A · 2004 to 2025
$45.5MSARS-CoV adaptations through a Systems Biology Lens (SYBIL)U19AI135972 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Adolfo Garcia-Sastre · 2018 to 2026
$27.2MRESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Melanie Maria Ott · 2018 to 2026
$21.4MX-ray Screening and Rapid Structure DeterminationP50AI150476 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EMERMAN, MICHAEL · 2019 to 2021
$14.4MDevelopment and Testing of New Computational Methods for Ligand Discovery and MechanismR35GM122481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian K Shoichet · 2017 to 2026
$8.5MPHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1MNovel VP30-host Interactions that Negatively Regulate Ebola Virus InfectionR01AI143292 · NIAID · WASHINGTON UNIVERSITY · PI AMARASINGHE, GAYA K., BASLER, CHRISTOPHER F · 2019 to 2023
$4.0MDiscovery of novel, ubiquitin-regulated mechanisms of TB control by macrophagesR01AI120694 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COX, JEFFERY S, KROGAN, NEVAN J · 2015 to 2019
$3.3MDecoding the Chlamydia inclusion membrane protein-host protein interactomeR01AI122747 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ENGEL, JOANNE N., KAAKE, ROBYN MIDORI · 2016 to 2020
$3.1MPharmaceutical Sciences and PharmacogenomicsT32GM142516 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Su Guo · 2022 to 2026
$2.4MInhibitors of the G protein GNAS which drives pancreatic tumorigenesisR01CA244550 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHOKAT, KEVAN M. · 2020 to 2024
$2.0MMolecular mechanisms of sigma receptor signalingR01GM119185 · NIGMS · HARVARD MEDICAL SCHOOL · PI KRUSE, ANDREW · 2017 to 2020
$1.3MNCI NIH HHS R01 CA244550NIAID NIH HHS HHSN272201400008CNIAID NIH HHS P01 AI063302NIAID NIH HHS P50 AI150476NIAID NIH HHS R01 AI120694NIAID NIH HHS R01 AI122747NIAID NIH HHS R01 AI143292NIAID NIH HHS U19 AI135972NIAID NIH HHS U19 AI135990NIGMS NIH HHS R01 GM119185NIGMS NIH HHS R35 GM122481NIGMS NIH HHS T32 GM007175NIGMS NIH HHS T32 GM142516
Abstract
Repurposing drugs as treatments for COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drawn much attention. Beginning with sigma receptor ligands and expanding to other drugs from screening in the field, we became concerned that phospholipidosis was a shared mechanism underlying the antiviral activity of many repurposed drugs. For all of the 23 cationic amphiphilic drugs we tested, including hydroxychloroquine, azithromycin, amiodarone, and four others already in clinical trials, phospholipidosis was monotonically correlated with antiviral efficacy. Conversely, drugs active against the same targets that did not induce phospholipidosis were not antiviral. Phospholipidosis depends on the physicochemical properties of drugs and does not reflect specific target-based activities-rather, it may be considered a toxic confound in early drug discovery. Early detection of phospholipidosis could eliminate these artifacts, enabling a focus on molecules with therapeutic potential.
Indexed as
COVID-19 Drug TreatmentDrug RepositioningA549 CellsAnimalsAntiviral AgentsCationsChlorocebus aethiopsCOVID-19Dose-Response Relationship, DrugFemaleHumansLipidosesMiceMicrobial Sensitivity TestsPhospholipidsSARS-CoV-2Antiviral AgentsCationsPhospholipidsSurface-Active Agents
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