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Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach

BACKGROUND: Similarities in the hijacking mechanisms used by SARS-CoV-2 and several types of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for cancer treatment. A recent study in cells infected with SARS-CoV-2 found a significant CK2 kin...

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Autores principales: Miranda, Jamilet, Bringas, Ricardo, Fernandez-de-Cossio, Jorge, Perera-Negrin, Yasser
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686809/
https://www.ncbi.nlm.nih.gov/pubmed/34930105
http://dx.doi.org/10.1186/s10020-021-00424-x
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author Miranda, Jamilet
Bringas, Ricardo
Fernandez-de-Cossio, Jorge
Perera-Negrin, Yasser
author_facet Miranda, Jamilet
Bringas, Ricardo
Fernandez-de-Cossio, Jorge
Perera-Negrin, Yasser
author_sort Miranda, Jamilet
collection PubMed
description BACKGROUND: Similarities in the hijacking mechanisms used by SARS-CoV-2 and several types of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for cancer treatment. A recent study in cells infected with SARS-CoV-2 found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses. CIGB-300, originally designed as an anticancer peptide, is an antagonist of CK2 kinase activity that binds to the CK2 phospho-acceptor sites. Recent preliminary results show the antiviral activity of CIGB-300 using a surrogate model of coronavirus. Here we present a computational biology study that provides evidence, at the molecular level, of how CIGB-300 may interfere with the SARS-CoV-2 life cycle within infected human cells. METHODS: Sequence analyses and data from phosphorylation studies were combined to predict infection-induced molecular mechanisms that can be interfered by CIGB-300. Next, we integrated data from multi-omics studies and data focusing on the antagonistic effect on the CK2 kinase activity of CIGB-300. A combination of network and functional enrichment analyses was used. RESULTS: Firstly, from the SARS-CoV studies, we inferred the potential incidence of CIGB-300 in SARS-CoV-2 interference on the immune response. Afterwards, from the analysis of multiple omics data, we proposed the action of CIGB-300 from the early stages of viral infections perturbing the virus hijacking of RNA splicing machinery. We also predicted the interference of CIGB-300 in virus-host interactions that are responsible for the high infectivity and the particular immune response to SARS-CoV-2 infection. Furthermore, we provided evidence of how CIGB-300 may participate in the attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders. CONCLUSIONS: Our computational analysis proposes putative molecular mechanisms that support the antiviral activity of CIGB-300. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-021-00424-x.
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spelling pubmed-86868092021-12-21 Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach Miranda, Jamilet Bringas, Ricardo Fernandez-de-Cossio, Jorge Perera-Negrin, Yasser Mol Med Research Article BACKGROUND: Similarities in the hijacking mechanisms used by SARS-CoV-2 and several types of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for cancer treatment. A recent study in cells infected with SARS-CoV-2 found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses. CIGB-300, originally designed as an anticancer peptide, is an antagonist of CK2 kinase activity that binds to the CK2 phospho-acceptor sites. Recent preliminary results show the antiviral activity of CIGB-300 using a surrogate model of coronavirus. Here we present a computational biology study that provides evidence, at the molecular level, of how CIGB-300 may interfere with the SARS-CoV-2 life cycle within infected human cells. METHODS: Sequence analyses and data from phosphorylation studies were combined to predict infection-induced molecular mechanisms that can be interfered by CIGB-300. Next, we integrated data from multi-omics studies and data focusing on the antagonistic effect on the CK2 kinase activity of CIGB-300. A combination of network and functional enrichment analyses was used. RESULTS: Firstly, from the SARS-CoV studies, we inferred the potential incidence of CIGB-300 in SARS-CoV-2 interference on the immune response. Afterwards, from the analysis of multiple omics data, we proposed the action of CIGB-300 from the early stages of viral infections perturbing the virus hijacking of RNA splicing machinery. We also predicted the interference of CIGB-300 in virus-host interactions that are responsible for the high infectivity and the particular immune response to SARS-CoV-2 infection. Furthermore, we provided evidence of how CIGB-300 may participate in the attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders. CONCLUSIONS: Our computational analysis proposes putative molecular mechanisms that support the antiviral activity of CIGB-300. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-021-00424-x. BioMed Central 2021-12-20 /pmc/articles/PMC8686809/ /pubmed/34930105 http://dx.doi.org/10.1186/s10020-021-00424-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Miranda, Jamilet
Bringas, Ricardo
Fernandez-de-Cossio, Jorge
Perera-Negrin, Yasser
Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach
title Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach
title_full Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach
title_fullStr Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach
title_full_unstemmed Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach
title_short Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach
title_sort targeting ck2 mediated signaling to impair/tackle sars-cov-2 infection: a computational biology approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686809/
https://www.ncbi.nlm.nih.gov/pubmed/34930105
http://dx.doi.org/10.1186/s10020-021-00424-x
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