Bivalent CK2 Inhibition as a Potent Strategy Against SARS-CoV-2 and Other Coronaviruses
Protein kinase CK2 (CK2), a ubiquitously expressed serine/threonine kinase, has emerged as a key host factor exploited by several viruses, including Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we investigate the role of CK2 subunits in SARS-CoV-2 replication and evaluate the antiviral potential and broad-spectrum anti-coronavirus activity of two CK2 inhibitors: the…
CK2, a serine/threonine kinase expressed in all cells, has been identified as a crucial viral host factor for several coronaviruses, including SARS-CoV-2. Researchers explored two CK2 inhibitors, CX-4945 and the newly developed bivalent inhibitor AB668, for their antiviral potential. Knockdown of CK2 subunits via siRNA significantly decreased SARS-CoV-2 replication, confirming its essential role in the virus's lifecycle.
Co-immunoprecipitation assays showed that SARS-CoV-2 nucleoprotein interacts with CK2, binding specifically to the tetrameric CK2 holoenzyme (CK22{beta}2) rather than individual subunits. AB668 demonstrated potent antiviral activity by targeting viral replication, effectively inhibiting both HCoV-OC43 and HCoV-229E. The study establishes CK2 as a critical factor for SARS-CoV-2 replication and highlights AB668 as a promising broad-spectrum antiviral candidate due to its high selectivity, minimal off-target effects, and efficacy against multiple coronaviruses.
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