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Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection

Ailyn C. Ramón, George V. Pérez, Evelin Caballero, Mauro Rosales, Daylén Aguilar, Dania Vázquez-Blomquist, Yassel Ramos, Arielis Rodríguez, Viviana Falcón, María P. Rodríguez, Yang Ke, Yasser Perera, View ORCID ProfileSilvio E. Perea
doi: https://doi.org/10.1101/2021.06.08.447588
Ailyn C. Ramón
1Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, Cuba
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George V. Pérez
1Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, Cuba
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Evelin Caballero
1Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, Cuba
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Mauro Rosales
1Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, Cuba
2Department of Animal and Human Biology, Faculty of Biology, University of Havana (UH), Havana 10400, Cuba
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Daylén Aguilar
1Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, Cuba
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Dania Vázquez-Blomquist
3Pharmacogenomic Group, Department of System Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba
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Yassel Ramos
4Mass Spectrometry Laboratory, Proteomics Group, Department of Systems Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba
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Arielis Rodríguez
4Mass Spectrometry Laboratory, Proteomics Group, Department of Systems Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba
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Viviana Falcón
5Microscopy Laboratory, Department of System Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba
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María P. Rodríguez
6Agricultural Research Department, Animal Biotechnology Division, CIGB, Havana 10600, Cuba
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Yang Ke
7China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Yongzhou Zhong Gu Biotechnology Co., Ltd, Lengshuitan District, Yongzhou City 425000, Hunan Province, China
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  • For correspondence: silvio.perea@cigb.edu.cu ypererapereranegrin@ccbjic.com young@ccbjic.com
Yasser Perera
1Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, Cuba
7China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Yongzhou Zhong Gu Biotechnology Co., Ltd, Lengshuitan District, Yongzhou City 425000, Hunan Province, China
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  • For correspondence: silvio.perea@cigb.edu.cu ypererapereranegrin@ccbjic.com young@ccbjic.com
Silvio E. Perea
1Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, Cuba
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  • ORCID record for Silvio E. Perea
  • For correspondence: silvio.perea@cigb.edu.cu ypererapereranegrin@ccbjic.com young@ccbjic.com
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Abstract

Coronaviruses constitute a global threat to human population since three highly pathogenic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have crossed species to cause severe human respiratory disease. Considering the worldwide emergency status due to the current COVID-19 pandemic, effective pan-coronavirus antiviral drugs are required to tackle the ongoing as well as future (re)emerging virus outbreaks. Protein kinase CK2 has been deemed a promising therapeutic target in COVID-19 supported by its in vitro pharmacologic inhibition and molecular studies on SARS-CoV-2 infected cells. CIGB-325 is a first-in-class synthetic peptide impairing the CK2-mediated signaling whose safety and clinical benefit have been evidenced in Covid-19 and cancer patients after intravenous administration. Here, we explored the putative antiviral effect of CIGB-325 over MDBK cells infected by bovine coronavirus (BCoV) Mebus. Importantly, CIGB-325 inhibited both the cytopathic effect and the number of plaques forming units with a half-inhibitory concentrations IC50 = 3.5 μM and 17.7 μM, respectively. Accordingly, viral protein accumulation at the cytoplasm was clearly reduced by treating BCoV-infected cells with CIGB-325 over time, as determined by immunocytochemistry. Of note, data from pull-down assay followed by western blot and/or mass spectrometry identification revealed physical interaction of CIGB-325 with nucleocapsid (N) protein and a bona fide cellular CK2 substrates. Functional enrichment and network analysis from the CIGB-325 interacting proteins indicated cytoskeleton reorganization and protein folding as the most represented biological processes disturbed by this anti-CK2 peptide. Altogether, our findings not only unveil the direct antiviral activity of CIGB-325 on coronavirus infection but also provide molecular clues underlying such effect. Also, our data reinforce the scientific rationality behind the pharmacologic inhibition of CK2 to treat coronavirus infections.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection
Ailyn C. Ramón, George V. Pérez, Evelin Caballero, Mauro Rosales, Daylén Aguilar, Dania Vázquez-Blomquist, Yassel Ramos, Arielis Rodríguez, Viviana Falcón, María P. Rodríguez, Yang Ke, Yasser Perera, Silvio E. Perea
bioRxiv 2021.06.08.447588; doi: https://doi.org/10.1101/2021.06.08.447588
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Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection
Ailyn C. Ramón, George V. Pérez, Evelin Caballero, Mauro Rosales, Daylén Aguilar, Dania Vázquez-Blomquist, Yassel Ramos, Arielis Rodríguez, Viviana Falcón, María P. Rodríguez, Yang Ke, Yasser Perera, Silvio E. Perea
bioRxiv 2021.06.08.447588; doi: https://doi.org/10.1101/2021.06.08.447588

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