tetano
Editor, Senior Moderator
Mol Med
. 2021 Dec 20;27(1):161.
doi: 10.1186/s10020-021-00424-x.
Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach
Jamilet Miranda[SUP] 1 [/SUP], Ricardo Bringas[SUP] 2 [/SUP], Jorge Fernandez-de-Cossio[SUP] 2 [/SUP], Yasser Perera-Negrin[SUP] 3 4 [/SUP]
Affiliations
Abstract
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.
Keywords: CIGB-300; CK2 inhibitor; Computational biology; Drug repurposing; HSBP1; NPM1/B23; Phosphoproteomics; SARS-CoV-2; SQSTM1; SRSF1.
. 2021 Dec 20;27(1):161.
doi: 10.1186/s10020-021-00424-x.
Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach
Jamilet Miranda[SUP] 1 [/SUP], Ricardo Bringas[SUP] 2 [/SUP], Jorge Fernandez-de-Cossio[SUP] 2 [/SUP], Yasser Perera-Negrin[SUP] 3 4 [/SUP]
Affiliations
- PMID: 34930105
- DOI: 10.1186/s10020-021-00424-x
Abstract
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.
Keywords: CIGB-300; CK2 inhibitor; Computational biology; Drug repurposing; HSBP1; NPM1/B23; Phosphoproteomics; SARS-CoV-2; SQSTM1; SRSF1.