CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner
Fig 9
The graphical depiction of CMPK2 inhibition of CoVs replication by interfering with their RdRp activities.
Upon CoV infection, IRF1 directly induces CMPK2 expression independently of the IFN-I pathway. CMPK2 localizes in mitochondria and provides sufficient substrate for Viperin-catalyzed production of ddhCTP through catalyzing the phosphorylation of CDP to produce CTP. Subsequently, ddhCTP directly stalls the progression of viral polymerase by competing with natural ribonucleotides. CMPK2, cytidine/uridine monophosphate kinase 2; CoV, coronavirus; ddhCTP, 3′-deoxy-3′,4′-didehydro-cytidine triphosphate; IFN-I, type I interferon; IRF1, interferon regulatory factor 1; RdRp, RNA-dependent RNA polymerase.