Alphaviruses are a group of globally distributed positive-sense RNA viruses which infect a variety of hosts including mosquitoes, birds, rodents and other mammals. They also constitue a potential threat to human health in many areas. Their viral replication machinery comprises four non-structural proteins (nsP1-4) produced as a single polyprotein. Structural domains comprising this superfamily share the structure of the N-terminal protease domain of alphavirus protein nsP2 (nsP2pro). This protein is a cysteine protease essential for viral replication and mediates the cytopathic effects (CPE) of the virus as it mediates the cleavage of the nsP1234 polyprotein replication complex into functional components. This domain shows ATPase and GTPase activity, RNA helicase activity and RNA 5'-triphosphatase activity and contains the catalytic dyad cysteine and histidine residues organized in a protein fold that differs significantly from any known cysteine protease or protein folds PMID:23010928,PMID:27030368,PMID:16962975.