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The Genome polyprotein of the Japanese Encephalitis Virus (JEV) is a massive precursor protein of approximately 3,400 amino acids that is cleaved by viral and host proteases into ten distinct functional proteins: three structural proteins (Capsid [C], Premembrane [prM], and Envelope [E]) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [3, 6]. This polyprotein serves as the central hub for the JEV life cycle, providing the structural components for the virion and the enzymatic machinery required for RNA replication and immune antagonism [1, 12]. The Envelope (E) protein is the primary mediator of host cell entry and the main target for vaccine-induced neutralizing antibodies [2, 15]. The non-structural enzymes, particularly the NS3 protease/helicase and the NS5 RNA-dependent RNA polymerase, are critical therapeutic targets because their inhibition directly halts viral replication [11, 16]. While there are no specific antiviral drugs currently licensed for Japanese encephalitis, various candidates such as remdesivir and nitazoxanide are being investigated for their ability to target these specific viral proteins [5, 9]. Management of the disease currently relies on preventative vaccination and supportive care to mitigate severe neurological symptoms [2, 4].
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