Radical S-adenosyl methionine domain-containing protein 2 (RSAD2)

Radical S-adenosyl methionine domain-containing protein 2 (RSAD2), widely known as viperin, is an interferon-inducible, antiviral enzyme that belongs to the S-adenosyl-L-methionine (SAM) superfamily[1][2][4][5]. It is primarily known for its broad-spectrum antiviral activity against many DNA and RNA viruses, including influenza, HIV-1, Zika virus, hepatitis C, cytomegalovirus, and others[1][2][4][5]. RSAD2 catalyzes the conversion of cytidine triphosphate (CTP) into 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) through a SAM-dependent radical mechanism, and this metabolite acts as a viral RNA chain terminator, thereby directly inhibiting viral replication[2][5]. In addition to its enzymatic antiviral function, RSAD2/viperin modulates innate immune signaling and is involved in the activation and differentiation of immune cells, such as plasmacytoid dendritic cells and CD4+ T cells[2][5]. Structurally, viperin localizes to the endoplasmic reticulum and lipid droplets; upon certain viral infections, it can also be found in mitochondria[1]. Viperin's activity is crucial for both type I and type II interferon-induced antiviral states[1][2][5].

Other names

ViperinS-adenosylmethionine-dependent nucleotide dehydratase RSAD2SANDCIG5Cig5Vig1Cytomegalovirus-induced gene 5 proteinVirus inhibitory protein, endoplasmic reticulum-associated, interferon-inducibleVirus-inhibitory protein, endoplasmic reticulum–associated, interferon-inducibleCig33

Inhibition of viral RNA-dependent RNA polymerases via production of 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), a nucleotide chain terminator; Inhibition of viral replication by disrupting formation of viral replication complexes; Disruption of lipid rafts affecting virus budding and release