Morphological cell profiling of SARS-CoV-2 infection identifies lactoferrin as candidate for COVID-19
dc.contributor.author | Carmen Mirabelli et eal. | |
dc.coverage.spatial | virtual | |
dc.date.accessioned | 2022-10-06T22:21:24Z | |
dc.date.available | 2022-10-06T22:21:24Z | |
dc.date.issued | 2021-09-07 | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.issn | 1091-6490 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/34413211 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/175000 | en |
dc.description.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. | |
dc.format.medium | ||
dc.publisher | Proceedings of the National Academy of Sciences | |
dc.rights | Licence for published version: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | COVID-19 | |
dc.subject | SARS-CoV-2 | |
dc.subject | drug repurposing screening | |
dc.subject | lactoferrin | |
dc.subject | Animals | |
dc.subject | Antiviral Agents | |
dc.subject | COVID-19 | |
dc.subject | Caco-2 Cells | |
dc.subject | Cell Line, Tumor | |
dc.subject | Chlorocebus aethiops | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Drug Discovery | |
dc.subject | Drug Repositioning | |
dc.subject | Epithelial Cells | |
dc.subject | Heparitin Sulfate | |
dc.subject | Hepatocytes | |
dc.subject | High-Throughput Screening Assays | |
dc.subject | Humans | |
dc.subject | Immunologic Factors | |
dc.subject | Lactoferrin | |
dc.subject | SARS-CoV-2 | |
dc.subject | Vero Cells | |
dc.subject | Virus Internalization | |
dc.subject | Virus Replication | |
dc.title | Morphological cell profiling of SARS-CoV-2 infection identifies lactoferrin as candidate for COVID-19 | |
dc.type | Conference Paper | |
dc.identifier.pmid | 34413211 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/175000/2/Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19.pdf | |
dc.identifier.doi | 10.1073/pnas.2105815118 | |
dc.identifier.doi | https://dx.doi.org/10.7302/6549 | |
dc.identifier.source | Proceedings of the National Academy of Sciences of the United States of America | |
dc.description.version | Published version | |
dc.date.updated | 2022-10-06T22:21:19Z | |
dc.identifier.volume | 118 | |
dc.identifier.issue | 36 | |
dc.identifier.startpage | e2105815118 | |
dc.identifier.name-orcid | al, Carmen Mirabelli et | |
dc.working.doi | 10.7302/6549 | en |
dc.owningcollname | Microbiology and Immunology, Department of |
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