宿主激酶CSNK2是包括SARS-CoV-2在内的致病性β冠状病毒的抑制靶点。
Host kinase CSNK2 is a target for inhibition of pathogenic β-coronaviruses including SARS-CoV-2.
作者信息
Yang Xuan, Dickmander Rebekah J, Bayati Armin, Taft-Benz Sharon A, Smith Jeffery L, Wells Carrow I, Madden Emily A, Brown Jason W, Lenarcic Erik M, Yount Boyd L, Chang Edcon, Axtman Alison D, Baric Ralph S, Heise Mark T, McPherson Peter S, Moorman Nathaniel J, Willson Timothy M
机构信息
Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Rapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, NC 27599, United States.
出版信息
bioRxiv. 2022 Jan 26:2022.01.03.474779. doi: 10.1101/2022.01.03.474779.
Inhibition of the protein kinase CSNK2 with any of 30 specific and selective inhibitors representing different chemotypes, blocked replication of pathogenic human and murine β-coronaviruses. The potency of in-cell CSNK2A target engagement across the set of inhibitors correlated with antiviral activity and genetic knockdown confirmed the essential role of the CSNK2 holoenzyme in β-coronavirus replication. Spike protein uptake was blocked by CSNK2A inhibition, indicating that antiviral activity was due in part to a suppression of viral entry. CSNK2A inhibition may be a viable target for development of new broad spectrum anti-β-coronavirus drugs.
用30种代表不同化学类型的特异性和选择性抑制剂中的任何一种抑制蛋白激酶CSNK2，均可阻断致病性人类和鼠类β冠状病毒的复制。在这组抑制剂中，细胞内CSNK2A靶点结合的效力与抗病毒活性相关，基因敲除证实了CSNK2全酶在β冠状病毒复制中的关键作用。CSNK2A抑制可阻断刺突蛋白摄取，表明抗病毒活性部分归因于对病毒进入的抑制。CSNK2A抑制可能是开发新型广谱抗β冠状病毒药物的一个可行靶点。
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