التفاصيل البيبلوغرافية
| العنوان: |
Drug repurposing platform for deciphering the druggable SARS-CoV-2 interactome |
| المؤلفون: |
Bogacheva, Mariia, Kuivanen, Suvi, Potdar, Swapnil, Hassinen, Antti, Huuskonen, Sini, Pöhner, Ina, Luck, Tamara J., Turunen, Laura, Feodoroff, Michaela, Szirovicza, Leonóra, Savijoki, Kirsi, Saarela, Jani, Tammela, Päivi, Paavolainen, Lassi, Poso, Antti, Varjosalo, Markku, Kallioniemi, Olli, Pietiäinen, Vilja, Vapalahti, Olli |
| المساهمون: |
Department of Virology, Medicum, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, Viral Zoonosis Research Unit, Institute of Biotechnology, Molecular Systems Biology, Division of Pharmaceutical Biosciences, Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, Bioactivity Screening Group, Bioimage Profiling, Precision Systems Medicine, Helsinki One Health (HOH), HUSLAB, Veterinary Microbiology and Epidemiology, Veterinary Biosciences, Olli Pekka Vapalahti / Principal Investigator, HUS Diagnostic Center |
| بيانات النشر: |
Elsevier Scientific Publ. Co |
| سنة النشر: |
2024 |
| المجموعة: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: |
11832 Microbiology and virology, 3121 General medicine, internal medicine and other clinical medicine, 317 Pharmacy |
| الوصف: |
The coronavirus disease 2019 (COVID-19) pandemic has heavily challenged the global healthcare system. Despite the vaccination programs, the new virus variants are circulating. Further research is required for understanding of the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and for discovery of therapeutic agents against the virus. Here, we took advantage of drug repurposing to identify if existing drugs could inhibit SARS-CoV-2 infection. We established an open high throughput platform for in vitro screening of drugs against SARS-CoV-2 infection. We screened similar to 1000 drugs for their ability to inhibit SARS-CoV-2-induced cell death in the African green monkey kidney cell line (Vero-E6), analyzed how the hit compounds affect the viral N (nucleocapsid) protein expression in human cell lines using high-content microscopic imaging and analysis, determined the hit drug targets in silico, and assessed their ability to cause phospholipidosis, which can interfere with the viral replication. Duvelisib was found by in silico interaction assay as a potential drug targeting virus-host protein interactions. The predicted interaction between PARP1 and S protein, affected by Duvelisib, was further validated by immunoprecipitation. Our results represent a rapidly applicable platform for drug repurposing and evaluation of the new emerging viruses' responses to the drugs. Further in silico studies help us to discover the druggable host pathways involved in the infectious cycle of SARS-CoV-2. ; Peer reviewed |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
The authors thank Minerva Institute (Helsinki, Finland) for providing utilities for the project; the FIMM High Throughput Biomedicine Unit for providing access to HT robotics, the FIMM High Content Imaging and Analysis Unit for HC imaging and analysis, and FIMM Genomics unit for genotyping services (HiLIFE, University of Helsinki and Biocenter Finland) . The authors acknowledge the CSC-IT Center for Science Ltd. for computational resources. The grants awarded by the Academy of Finland [grant numbers iCOIN-336496: OK, VP, OV; FIRI 2020-337036: FIMM-HCA, AH, VP] , the EU H2020 VEO project (OV) , Juho Vainio foundation, anonymous donors through Helsinki University Research funds (OV) and Minerva Foundation for the COVID19 research project grant (VP) are also greatly acknowledged. The authors thank Katja Rosti, University of Helsinki, Dr. Petri Saviranta, and Sirpa Jylha , VTT, Finland for the supply of 7A12 antibodies against SARS-CoV-2 S protein. The authors thank Prof. Kari Alitalo for providing a fluorescence reader at BSL-3 and Alyce Whipp for checking the English language grammar in the manuscript.; Bogacheva , M , Kuivanen , S , Potdar , S , Hassinen , A , Huuskonen , S , Pöhner , I , Luck , T J , Turunen , L , Feodoroff , M , Szirovicza , L , Savijoki , K , Saarela , J , Tammela , P , Paavolainen , L , Poso , A , Varjosalo , M , Kallioniemi , O , Pietiäinen , V & Vapalahti , O 2024 , ' Drug repurposing platform for deciphering the druggable SARS-CoV-2 interactome ' , Antiviral Research , vol. 223 , 105813 . https://doi.org/10.1016/j.antiviral.2024.105813Test; ORCID: /0000-0001-7306-7175/work/152924410; ORCID: /0000-0003-2270-6824/work/152925170; ORCID: /0000-0003-3125-2406/work/152926687; ORCID: /0000-0003-4697-8066/work/152926723; ORCID: /0000-0003-1528-044X/work/152927229; ORCID: /0000-0002-1340-9732/work/152927567; ORCID: /0000-0002-6094-9838/work/152928335; ORCID: /0000-0003-3857-1805/work/152931879; ORCID: /0000-0001-9491-2868/work/152932584; ORCID: /0000-0002-9859-1261/work/152932735; ORCID: /0000-0003-1508-2718/work/152933216; ORCID: /0000-0002-2778-6918/work/152933252; ORCID: /0000-0001-6608-1120/work/152933672; ORCID: /0000-0003-0274-4794/work/155648905; http://hdl.handle.net/10138/571055Test; 05032077-daad-4120-a874-3c60fa96febb; 001177707500001 |
| الإتاحة: |
http://hdl.handle.net/10138/571055Test |
| حقوق: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| رقم الانضمام: |
edsbas.3DA487A1 |
| قاعدة البيانات: |
BASE |
