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

Ramon, A. C.; Perez, G. V.; Caballero, E.; Rosales, M.; Aguilar, D.; Vazquez-Blomquist, D. M.; Ramos, Y.; Rodriguez, A.; Falcon, V.; Rodriguez, M. P.; Ke, Y.; Perera, Y.; Perea, S. E.

doi:10.1101/2021.06.08.447588

bioRxiv · 10.1101/2021.06.08.447588

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

Ramon, A. C.·Perez, G. V.·Caballero, E.·Rosales, M.·Aguilar, D.·Vazquez-Blomquist, D. M.·Ramos, Y.·Rodriguez, A.·Falcon, V.·Rodriguez, M. P.·Ke, Y.·Perera, Y.·Perea, S. E.

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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 M and 17.7 M, 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.

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Ramon, A. C., Perez, G. V., Caballero, E., Rosales, M., Aguilar, D., Vazquez-Blomquist, D. M., Ramos, Y., Rodriguez, A., Falcon, V., Rodriguez, M. P., Ke, Y., Perera, Y., Perea, S. E.. 2021-06-08. Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection. https://doi.org/10.1101/2021.06.08.447588

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