Japanese encephalitis virus non-structural protein 3 (NS3) (JEV NS3)

JEV NS3 is a large, multifunctional protein of approximately 619 amino acids that is indispensable for the replication and pathogenesis of the Japanese encephalitis virus [1.1.1, 1.3.2]. It possesses two distinct enzymatic regions: an N-terminal serine protease domain and a C-terminal domain with RNA helicase and nucleoside triphosphatase (NTPase) activities [1.1.1, 1.2.1]. The protease domain, in complex with its essential cofactor NS2B, catalyzes the proteolytic processing of the viral polyprotein at specific junctions, which is a prerequisite for the assembly of the viral replication complex [1.1.2, 1.3.4]. The helicase domain utilizes energy from ATP hydrolysis to unwind double-stranded RNA intermediates, facilitating the synthesis of new viral genomes [1.1.1, 1.2.1]. Additionally, NS3 is involved in subverting host innate immunity and inducing neuronal apoptosis, which are key factors in the development of severe encephalitis [1.1.2, 1.4.3]. Due to its central role in the viral life cycle, NS3 is a major focus for the development of small-molecule inhibitors, including protease and helicase antagonists, aimed at treating JEV infections [1.2.2, 1.2.4].

Other names

Non-structural protein 3JEV NS3 proteaseJEV NS3 helicaseNS3 proteinSerine protease NS3Genome polyprotein NS3

Inhibition of the NS2B-NS3 serine protease activity to prevent polyprotein processing, or inhibition of the NS3 helicase/NTPase activity to block viral RNA unwinding and replication.