Drug repurposing platform for deciphering the druggable SARS-CoV-2 interactome
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
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 ∼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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:223 |
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| Enthalten in: |
Antiviral research - 223(2024) vom: 15. März, Seite 105813 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bogacheva, Mariia S [VerfasserIn] |
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| Links: |
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| Themen: |
COVID-19 |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.antiviral.2024.105813 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 ∼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 | ||
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| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Drug repurposing | |
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| 700 | 1 | |a Kuivanen, Suvi |e verfasserin |4 aut | |
| 700 | 1 | |a Potdar, Swapnil |e verfasserin |4 aut | |
| 700 | 1 | |a Hassinen, Antti |e verfasserin |4 aut | |
| 700 | 1 | |a Huuskonen, Sini |e verfasserin |4 aut | |
| 700 | 1 | |a Pöhner, Ina |e verfasserin |4 aut | |
| 700 | 1 | |a Luck, Tamara J |e verfasserin |4 aut | |
| 700 | 1 | |a Turunen, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Feodoroff, Michaela |e verfasserin |4 aut | |
| 700 | 1 | |a Szirovicza, Leonora |e verfasserin |4 aut | |
| 700 | 1 | |a Savijoki, Kirsi |e verfasserin |4 aut | |
| 700 | 1 | |a Saarela, Jani |e verfasserin |4 aut | |
| 700 | 1 | |a Tammela, Päivi |e verfasserin |4 aut | |
| 700 | 1 | |a Paavolainen, Lassi |e verfasserin |4 aut | |
| 700 | 1 | |a Poso, Antti |e verfasserin |4 aut | |
| 700 | 1 | |a Varjosalo, Markku |e verfasserin |4 aut | |
| 700 | 1 | |a Kallioniemi, Olli |e verfasserin |4 aut | |
| 700 | 1 | |a Pietiäinen, Vilja |e verfasserin |4 aut | |
| 700 | 1 | |a Vapalahti, Olli |e verfasserin |4 aut | |
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