Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection
| Autor: | Yang Ke, Ailyn C. Ramón, Viviana Falcón, Daylen Aguilar, Silvio E. Perea, Dania Marcia Vazquez-Blomquist, George V. Pérez, Evelin Caballero, Maria Pilar Rodriguez, Mauro Rosales, Yassel Ramos, Arielis Rodriguez, Yasser Perera |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Coronavirus
Bovine education.field_of_study medicine.diagnostic_test Viral protein Population Biology medicine.disease_cause Virology Antiviral Agents Virus In vitro Infectious Diseases Western blot medicine Animals Cattle Phosphorylation education Casein Kinase II Peptides bovine coronavirus protein kinase CK2 kinase inhibitor CIGB-325 Bovine coronavirus Coronavirus Cytopathic effect |
| Zdroj: | Viruses; Volume 14; Issue 3; Pages: 552 |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v14030552 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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