ArticleProceedings of the National Academy of Sciences of the United States of America2021
Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
144 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.
- The effects of orally administered lactoferrin in the prevention and management of viral infections: A systematic review.Reviews in medical virology · 2022Pooled it
- Supporting respiratory epithelia and lowering inflammation to effectively treat common cold symptoms: A randomized controlled trial.PloS one · 2024Trial
- Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial.Nutrients · 2023Trial
- A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care.Annals of medicine · 2023Trial
- Lactoferrin blocks orthopoxvirus entry via heparan sulphate and regulates host antiviral pathways.Emerging microbes & infections · 2026Article
- A host-centric morphological profiling approach to identify repurposed antiviral drugs.iScience · 2026Article
- Evaluation of artificial intelligence identified ipratropium bromide for the treatment of coronavirus disease 2019.Scientific reports · 2026Article
- PhenoProfiler: advancing phenotypic learning for image-based drug discovery.Nature communications · 2025Article
- Prediction of mixture toxicity of essential oil constituents using nonparametric and parametric models against Musca domestica L.Pest management science · 2025Article
- Review
- Lactoferrin and SIgA Concentrations in Human Milk of SARS-CoV-Infected Mothers-Polish Cohort Study.Nutrients · 2025Article
- Morphological profiling data resource enables prediction of chemical compound properties.iScience · 2025Article
- In vitro efficacy of bovine lactoferrin against bovine viral diarrhea virus.Archives of microbiology · 2025Article
- Anticancer potential of lactoferrin: effects, drug synergy and molecular interactions.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
- Self-supervision advances morphological profiling by unlocking powerful image representations.Scientific reports · 2025Article
- Lactoferrin exhibits PEDV antiviral activity by interfering with spike-heparan sulfate proteoglycans binding and activating mucosal immune response.Veterinary research · 2025Article
- Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1.Scientific reports · 2025Article
- Semisupervised Contrastive Learning for Bioactivity Prediction Using Cell Painting Image Data.Journal of chemical information and modeling · 2025Article
- Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.Stem cell reports · 2025Article
- Nutrition, production, and processing of virgin omega-3 polyunsaturated fatty acids in dairy: An integrative review.Heliyon · 2024Review
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly identified and translated to clinical care. Traditional drug discovery methods have a >90% failure rate and can take 10 to 15 y from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious agents against SARS-CoV-2. From a library of 1,425 US Food and Drug Administration (FDA)-approved compounds and clinical candidates, we identified 17 hits that inhibited SARS-CoV-2 infection and analyzed their antiviral activity across multiple cell lines, including lymph node carcinoma of the prostate (LNCaP) cells and a physiologically relevant model of alveolar epithelial type 2 cells (iAEC2s). Additionally, we found that inhibitors of the Ras/Raf/MEK/ERK signaling pathway exacerbate SARS-CoV-2 infection in vitro. Notably, we discovered that lactoferrin, a glycoprotein found in secretory fluids including mammalian milk, inhibits SARS-CoV-2 infection in the nanomolar range in all cell models with multiple modes of action, including blockage of virus attachment to cellular heparan sulfate and enhancement of interferon responses. Given its safety profile, lactoferrin is a readily translatable therapeutic option for the management of COVID-19.
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Registered trials
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.