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Identifying FDA-approved drugs with multimodal properties against COVID-19 using a data-driven approach and a lung organoid model of SARS-CoV-2 entry
- Source :
- Molecular Medicine, Vol 27, Iss 1, Pp 1-11 (2021), Molecular Medicine, Duarte, R R R, Copertino, D, Iñiguez, L, Marston, J, Bram, Y, Han, Y, Schwartz, R, Chen, S, Nixon, D & Powell, T R 2021, ' Identifying FDA-approved drugs with multimodal properties against COVID-19 using a data-driven approach and a lung organoid model of SARS-CoV-2 entry ', Molecular Medicine, vol. 27, no. 1, 105 . https://doi.org/10.1186/s10020-021-00356-6
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background Vaccination programs have been launched worldwide to halt the spread of COVID-19. However, the identification of existing, safe compounds with combined treatment and prophylactic properties would be beneficial to individuals who are waiting to be vaccinated, particularly in less economically developed countries, where vaccine availability may be initially limited. Methods We used a data-driven approach, combining results from the screening of a large transcriptomic database (L1000) and molecular docking analyses, with in vitro tests using a lung organoid model of SARS-CoV-2 entry, to identify drugs with putative multimodal properties against COVID-19. Results Out of thousands of FDA-approved drugs considered, we observed that atorvastatin was the most promising candidate, as its effects negatively correlated with the transcriptional changes associated with infection. Atorvastatin was further predicted to bind to SARS-CoV-2’s main protease and RNA-dependent RNA polymerase, and was shown to inhibit viral entry in our lung organoid model. Conclusions Small clinical studies reported that general statin use, and specifically, atorvastatin use, are associated with protective effects against COVID-19. Our study corroborrates these findings and supports the investigation of atorvastatin in larger clinical studies. Ultimately, our framework demonstrates one promising way to fast-track the identification of compounds for COVID-19, which could similarly be applied when tackling future pandemics.
- Subjects :
- Atorvastatin
Connectivity mapping
Bioinformatics
Biochemistry
Medicine
Drug Approval
Lung
Genetics (clinical)
Coronavirus 3C Proteases
Coronavirus RNA-Dependent RNA Polymerase
Lung organoids
Trifluoperazine
Vaccination
Molecular Docking Simulation
Organoids
Drug repositioning
medicine.anatomical_structure
Drug screening
Doxycycline
Molecular docking
Spike Glycoprotein, Coronavirus
Molecular Medicine
medicine.drug
Research Article
Coronavirus disease 2019 (COVID-19)
RM1-950
QD415-436
Antiviral Agents
Models, Biological
Cell Line
Viral entry
Genetics
Organoid
Humans
Molecular Biology
Pandemic
business.industry
SARS-CoV-2
United States Food and Drug Administration
COVID-19
Drug testing
Chemoinformatics
Vesiculovirus
Virus Internalization
Molecular medicine
United States
COVID-19 Drug Treatment
Gene Expression Regulation
Raloxifene Hydrochloride
Therapeutics. Pharmacology
business
Subjects
Details
- Language :
- English
- ISSN :
- 15283658 and 10761551
- Volume :
- 27
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine
- Accession number :
- edsair.doi.dedup.....0b5e5058b3ef59aa569cff928e4c65a2
- Full Text :
- https://doi.org/10.1186/s10020-021-00356-6