Cargando…

Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis

BACKGROUND: The coronavirus disease-19 (COVID-19) emerged in Wuhan, China and rapidly spread worldwide. Researchers are trying to find a way to treat this disease as soon as possible. The present study aimed to identify the genes involved in COVID-19 and find a new drug target therapy. Currently, th...

Descripción completa

Detalles Bibliográficos
Autores principales: Adhami, Masoumeh, Sadeghi, Balal, Rezapour, Ali, Haghdoost, Ali Akbar, MotieGhader, Habib
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952507/
https://www.ncbi.nlm.nih.gov/pubmed/33711981
http://dx.doi.org/10.1186/s12896-021-00680-z
_version_ 1783663741222518784
author Adhami, Masoumeh
Sadeghi, Balal
Rezapour, Ali
Haghdoost, Ali Akbar
MotieGhader, Habib
author_facet Adhami, Masoumeh
Sadeghi, Balal
Rezapour, Ali
Haghdoost, Ali Akbar
MotieGhader, Habib
author_sort Adhami, Masoumeh
collection PubMed
description BACKGROUND: The coronavirus disease-19 (COVID-19) emerged in Wuhan, China and rapidly spread worldwide. Researchers are trying to find a way to treat this disease as soon as possible. The present study aimed to identify the genes involved in COVID-19 and find a new drug target therapy. Currently, there are no effective drugs targeting SARS-CoV-2, and meanwhile, drug discovery approaches are time-consuming and costly. To address this challenge, this study utilized a network-based drug repurposing strategy to rapidly identify potential drugs targeting SARS-CoV-2. To this end, seven potential drugs were proposed for COVID-19 treatment using protein-protein interaction (PPI) network analysis. First, 524 proteins in humans that have interaction with the SARS-CoV-2 virus were collected, and then the PPI network was reconstructed for these collected proteins. Next, the target miRNAs of the mentioned module genes were separately obtained from the miRWalk 2.0 database because of the important role of miRNAs in biological processes and were reported as an important clue for future analysis. Finally, the list of the drugs targeting module genes was obtained from the DGIDb database, and the drug-gene network was separately reconstructed for the obtained protein modules. RESULTS: Based on the network analysis of the PPI network, seven clusters of proteins were specified as the complexes of proteins which are more associated with the SARS-CoV-2 virus. Moreover, seven therapeutic candidate drugs were identified to control gene regulation in COVID-19. PACLITAXEL, as the most potent therapeutic candidate drug and previously mentioned as a therapy for COVID-19, had four gene targets in two different modules. The other six candidate drugs, namely, BORTEZOMIB, CARBOPLATIN, CRIZOTINIB, CYTARABINE, DAUNORUBICIN, and VORINOSTAT, some of which were previously discovered to be efficient against COVID-19, had three gene targets in different modules. Eventually, CARBOPLATIN, CRIZOTINIB, and CYTARABINE drugs were found as novel potential drugs to be investigated as a therapy for COVID-19. CONCLUSIONS: Our computational strategy for predicting repurposable candidate drugs against COVID-19 provides efficacious and rapid results for therapeutic purposes. However, further experimental analysis and testing such as clinical applicability, toxicity, and experimental validations are required to reach a more accurate and improved treatment. Our proposed complexes of proteins and associated miRNAs, along with discovered candidate drugs might be a starting point for further analysis by other researchers in this urgency of the COVID-19 pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12896-021-00680-z.
format Online
Article
Text
id pubmed-7952507
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-79525072021-03-12 Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis Adhami, Masoumeh Sadeghi, Balal Rezapour, Ali Haghdoost, Ali Akbar MotieGhader, Habib BMC Biotechnol Research Article BACKGROUND: The coronavirus disease-19 (COVID-19) emerged in Wuhan, China and rapidly spread worldwide. Researchers are trying to find a way to treat this disease as soon as possible. The present study aimed to identify the genes involved in COVID-19 and find a new drug target therapy. Currently, there are no effective drugs targeting SARS-CoV-2, and meanwhile, drug discovery approaches are time-consuming and costly. To address this challenge, this study utilized a network-based drug repurposing strategy to rapidly identify potential drugs targeting SARS-CoV-2. To this end, seven potential drugs were proposed for COVID-19 treatment using protein-protein interaction (PPI) network analysis. First, 524 proteins in humans that have interaction with the SARS-CoV-2 virus were collected, and then the PPI network was reconstructed for these collected proteins. Next, the target miRNAs of the mentioned module genes were separately obtained from the miRWalk 2.0 database because of the important role of miRNAs in biological processes and were reported as an important clue for future analysis. Finally, the list of the drugs targeting module genes was obtained from the DGIDb database, and the drug-gene network was separately reconstructed for the obtained protein modules. RESULTS: Based on the network analysis of the PPI network, seven clusters of proteins were specified as the complexes of proteins which are more associated with the SARS-CoV-2 virus. Moreover, seven therapeutic candidate drugs were identified to control gene regulation in COVID-19. PACLITAXEL, as the most potent therapeutic candidate drug and previously mentioned as a therapy for COVID-19, had four gene targets in two different modules. The other six candidate drugs, namely, BORTEZOMIB, CARBOPLATIN, CRIZOTINIB, CYTARABINE, DAUNORUBICIN, and VORINOSTAT, some of which were previously discovered to be efficient against COVID-19, had three gene targets in different modules. Eventually, CARBOPLATIN, CRIZOTINIB, and CYTARABINE drugs were found as novel potential drugs to be investigated as a therapy for COVID-19. CONCLUSIONS: Our computational strategy for predicting repurposable candidate drugs against COVID-19 provides efficacious and rapid results for therapeutic purposes. However, further experimental analysis and testing such as clinical applicability, toxicity, and experimental validations are required to reach a more accurate and improved treatment. Our proposed complexes of proteins and associated miRNAs, along with discovered candidate drugs might be a starting point for further analysis by other researchers in this urgency of the COVID-19 pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12896-021-00680-z. BioMed Central 2021-03-12 /pmc/articles/PMC7952507/ /pubmed/33711981 http://dx.doi.org/10.1186/s12896-021-00680-z Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Adhami, Masoumeh
Sadeghi, Balal
Rezapour, Ali
Haghdoost, Ali Akbar
MotieGhader, Habib
Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis
title Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis
title_full Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis
title_fullStr Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis
title_full_unstemmed Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis
title_short Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis
title_sort repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952507/
https://www.ncbi.nlm.nih.gov/pubmed/33711981
http://dx.doi.org/10.1186/s12896-021-00680-z
work_keys_str_mv AT adhamimasoumeh repurposingnoveltherapeuticcandidatedrugsforcoronavirusdisease19basedonproteinproteininteractionnetworkanalysis
AT sadeghibalal repurposingnoveltherapeuticcandidatedrugsforcoronavirusdisease19basedonproteinproteininteractionnetworkanalysis
AT rezapourali repurposingnoveltherapeuticcandidatedrugsforcoronavirusdisease19basedonproteinproteininteractionnetworkanalysis
AT haghdoostaliakbar repurposingnoveltherapeuticcandidatedrugsforcoronavirusdisease19basedonproteinproteininteractionnetworkanalysis
AT motieghaderhabib repurposingnoveltherapeuticcandidatedrugsforcoronavirusdisease19basedonproteinproteininteractionnetworkanalysis