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-Ulloa,
Viviana Falcón,
María Pilar Rodríguez-Moltó,
Ke Yang,
Yasser Perera,
Silvio E. Perea
Affiliations
Ailyn C. Ramón
Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
George V. Pérez
Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Evelin Caballero
Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Mauro Rosales
Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Daylén Aguilar
Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Dania Vázquez-Blomquist
Pharmacogenomic Group, Department of System Biology, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Yassel Ramos
Mass Spectrometry Laboratory, Proteomics Group, Department of Systems Biology, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Arielis Rodríguez-Ulloa
Mass Spectrometry Laboratory, Proteomics Group, Department of Systems Biology, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Viviana Falcón
Microscopy Laboratory, Department of System Biology, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
María Pilar Rodríguez-Moltó
Department of Agricultural Research, Animal Biotechnology Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Ke Yang
China-Cuba Biotechnology Joint Innovation Center, Yongzhou Zhong Gu Biotechnology, Yongzhou 425000, China
Yasser Perera
Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Silvio E. Perea
Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba
Coronaviruses constitute a global threat to the human population; therefore, effective pan-coronavirus antiviral drugs are required to tackle future re-emerging virus outbreaks. Protein kinase CK2 has been suggested as a promising therapeutic target in COVID-19 owing to the in vitro antiviral activity observed after both pharmacologic and genetic inhibition of the enzyme. Here, we explored the putative antiviral effect of the anti-CK2 peptide CIGB-325 on bovine coronavirus (BCoV) infection using different in vitro viral infected cell-based assays. The impact of the peptide on viral mRNA and protein levels was determined by qRT-PCR and Western blot, respectively. Finally, pull-down experiments followed by Western blot and/or mass spectrometry analysis were performed to identify CIGB-325-interacting proteins. We found that CIGB-325 inhibited both the cytopathic effect and the number of plaque-forming units. Accordingly, intracellular viral protein levels were clearly reduced after treatment of BCoV-infected cells, with CIGB-325 determined by immunocytochemistry. Pull-down assay data revealed the physical interaction of CIGB-325 with viral nucleocapsid (N) protein and a group of bona fide CK2 cellular substrates. Our findings evidence in vitro antiviral activity of CIGB-325 against bovine coronavirus as well as some molecular clues that might support such effect. Altogether, data provided here strengthen the rationale of inhibiting CK2 to treat betacoronavirus infections.
