Molecular and biochemical properties of viperin. (a) Genetic organization of VIPERIN. The VIPERIN gene is located in the short arm of chromosome 2 and found adjacent to and inverted with respect to CMPK2. The gene lncRNA-CMPK2 is located adjacent to CMPK2 and acts as a negative regulator for CMPK2 levels. (b) Previously described domains of the viperin protein. The three predicted domains of viperin and their reported roles are shown. (c) Production of ddhCTP. The mitochondrial kinase CMPK2 catalyzes the phosphorylation of CDP to produce CTP, which can then be used as a substrate by viperin to produce ddhCTP. For a detailed mechanistic proposal for viperin catalysis, see Reference 1. (d) Crystal structure of mouse viperin in complex with SAH and its substrate CTP showing the RS and C-terminal domains are not isolable (6Q2P). Abbreviations: CDP, cytidine diphosphate; CIA, cytosolic iron-sulfur protein assembly; CTP, cytidine triphosphate; ddhCTP, 3′-deoxy-3′,4′-didehydro-cytidine triphosphate; DENV-2, dengue virus serotype-2; ER, endoplasmic reticulum; HCV, hepatitis C virus; LD, lipid droplet; RS, radical S-adenosyl-L-methionine; SAH, S-adenosylhomocysteine; SAM, S-adenosyl-L-methionine; ZIKV, Zika virus.