A phenomics approach for antiviral drug discovery
Abstract Background The emergence and continued global spread of the current COVID-19 pandemic has highlighted the need for methods to identify novel or repurposed therapeutic drugs in a fast and effective way. Despite the availability of methods for the discovery of antiviral drugs, the majority te...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-021-01086-1 |
| _version_ | 1818832867526967296 |
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| author | Jonne Rietdijk Marianna Tampere Aleksandra Pettke Polina Georgiev Maris Lapins Ulrika Warpman-Berglund Ola Spjuth Marjo-Riitta Puumalainen Jordi Carreras-Puigvert |
| author_facet | Jonne Rietdijk Marianna Tampere Aleksandra Pettke Polina Georgiev Maris Lapins Ulrika Warpman-Berglund Ola Spjuth Marjo-Riitta Puumalainen Jordi Carreras-Puigvert |
| author_sort | Jonne Rietdijk |
| collection | DOAJ |
| description | Abstract Background The emergence and continued global spread of the current COVID-19 pandemic has highlighted the need for methods to identify novel or repurposed therapeutic drugs in a fast and effective way. Despite the availability of methods for the discovery of antiviral drugs, the majority tend to focus on the effects of such drugs on a given virus, its constituent proteins, or enzymatic activity, often neglecting the consequences on host cells. This may lead to partial assessment of the efficacy of the tested anti-viral compounds, as potential toxicity impacting the overall physiology of host cells may mask the effects of both viral infection and drug candidates. Here we present a method able to assess the general health of host cells based on morphological profiling, for untargeted phenotypic drug screening against viral infections. Results We combine Cell Painting with antibody-based detection of viral infection in a single assay. We designed an image analysis pipeline for segmentation and classification of virus-infected and non-infected cells, followed by extraction of morphological properties. We show that this methodology can successfully capture virus-induced phenotypic signatures of MRC-5 human lung fibroblasts infected with human coronavirus 229E (CoV-229E). Moreover, we demonstrate that our method can be used in phenotypic drug screening using a panel of nine host- and virus-targeting antivirals. Treatment with effective antiviral compounds reversed the morphological profile of the host cells towards a non-infected state. Conclusions The phenomics approach presented here, which makes use of a modified Cell Painting protocol by incorporating an anti-virus antibody stain, can be used for the unbiased morphological profiling of virus infection on host cells. The method can identify antiviral reference compounds, as well as novel antivirals, demonstrating its suitability to be implemented as a strategy for antiviral drug repurposing and drug discovery. |
| first_indexed | 2024-12-19T02:09:51Z |
| format | Article |
| id | doaj.art-9068f8fd2df24d619691a2135b248fc7 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-19T02:09:51Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-9068f8fd2df24d619691a2135b248fc72022-12-21T20:40:49ZengBMCBMC Biology1741-70072021-08-0119111510.1186/s12915-021-01086-1A phenomics approach for antiviral drug discoveryJonne Rietdijk0Marianna Tampere1Aleksandra Pettke2Polina Georgiev3Maris Lapins4Ulrika Warpman-Berglund5Ola Spjuth6Marjo-Riitta Puumalainen7Jordi Carreras-Puigvert8Department of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala UniversityDepartment of Oncology and Pathology and Science for Life Laboratory, Karolinska InstitutetDepartment of Oncology and Pathology and Science for Life Laboratory, Karolinska InstitutetDepartment of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala UniversityDepartment of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala UniversityDepartment of Oncology and Pathology and Science for Life Laboratory, Karolinska InstitutetDepartment of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala UniversityDepartment of Oncology and Pathology and Science for Life Laboratory, Karolinska InstitutetDepartment of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala UniversityAbstract Background The emergence and continued global spread of the current COVID-19 pandemic has highlighted the need for methods to identify novel or repurposed therapeutic drugs in a fast and effective way. Despite the availability of methods for the discovery of antiviral drugs, the majority tend to focus on the effects of such drugs on a given virus, its constituent proteins, or enzymatic activity, often neglecting the consequences on host cells. This may lead to partial assessment of the efficacy of the tested anti-viral compounds, as potential toxicity impacting the overall physiology of host cells may mask the effects of both viral infection and drug candidates. Here we present a method able to assess the general health of host cells based on morphological profiling, for untargeted phenotypic drug screening against viral infections. Results We combine Cell Painting with antibody-based detection of viral infection in a single assay. We designed an image analysis pipeline for segmentation and classification of virus-infected and non-infected cells, followed by extraction of morphological properties. We show that this methodology can successfully capture virus-induced phenotypic signatures of MRC-5 human lung fibroblasts infected with human coronavirus 229E (CoV-229E). Moreover, we demonstrate that our method can be used in phenotypic drug screening using a panel of nine host- and virus-targeting antivirals. Treatment with effective antiviral compounds reversed the morphological profile of the host cells towards a non-infected state. Conclusions The phenomics approach presented here, which makes use of a modified Cell Painting protocol by incorporating an anti-virus antibody stain, can be used for the unbiased morphological profiling of virus infection on host cells. The method can identify antiviral reference compounds, as well as novel antivirals, demonstrating its suitability to be implemented as a strategy for antiviral drug repurposing and drug discovery.https://doi.org/10.1186/s12915-021-01086-1PhenomicsMorphological profilingCell PaintingDrug discoveryAntiviral |
| spellingShingle | Jonne Rietdijk Marianna Tampere Aleksandra Pettke Polina Georgiev Maris Lapins Ulrika Warpman-Berglund Ola Spjuth Marjo-Riitta Puumalainen Jordi Carreras-Puigvert A phenomics approach for antiviral drug discovery BMC Biology Phenomics Morphological profiling Cell Painting Drug discovery Antiviral |
| title | A phenomics approach for antiviral drug discovery |
| title_full | A phenomics approach for antiviral drug discovery |
| title_fullStr | A phenomics approach for antiviral drug discovery |
| title_full_unstemmed | A phenomics approach for antiviral drug discovery |
| title_short | A phenomics approach for antiviral drug discovery |
| title_sort | phenomics approach for antiviral drug discovery |
| topic | Phenomics Morphological profiling Cell Painting Drug discovery Antiviral |
| url | https://doi.org/10.1186/s12915-021-01086-1 |
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