Uncage hijacked kinases from SARS-CoV-2 interactions

Kinases are versatile signaling nodes and thus represent a central target for viruses to reprogram the host cell for their needs. SARS-CoV-2 efficiently hijacks this crucial cellular control mechanism for ensuring their optimal propagation. We assume that targeting druggable kinase activities may alter SARS-CoV-2:host-protein interactions and functions. We bear the hope that targeting a hijacked host kinase may reduce virus assembly and/or pathological implications for cellular functions. We aim to validate and chemically target interdependencies emanating from two kinase cascades with viral proteins directly in human pulmonary cell lines. First, we apply a cell-based kinase conformation (KinCon) reporter for determining enzyme activity changes upon transient and viral expression of selected viral SARS-Cov-2 proteins. Second, we define the impact of kinase-directed small molecules (activators/inhibitors) on cellular SARS-CoV-2 functions. Third, we focus on modulating the cAMP-PKA and MAPK pathways to determine consequences on the effectiveness of virus assembly and function. Vaccines for combating SARS-CoV-2 infections save thousands of lives. Mutations may hamper their efficacies. We bear the hope that targeting host kinases may become part of COVID-19 and mutation-decoupled therapy approaches.