Recent Advances in Antivirals for Japanese Encephalitis Virus

Abstract

Culex mosquitoes are the primary vectors of the Japanese encephalitis virus (JEV). Since its discovery in 1935, Japanese encephalitis (JE), caused by JEV, has posed a significant threat to human health. Despite the widespread implementation of several JEV vaccines, the transmission chain of JEV in the natural ecosystem has not changed, and the vector of transmission cannot be eradicated. Therefore, JEV is still the focus of attention for flaviviruses. At present, there is no clinically specific drug for JE treatment. JEV infection is a complex interaction between the virus and the host cell, which is the focus of drug design and development. An overview of antivirals that target JEV elements and host factors is presented in this review. In addition, drugs that balance antiviral effects and host protection by regulating innate immunity, inflammation, apoptosis, or necrosis are reviewed to treat JE effectively.

Current Advances in Japanese Encephalitis Virus Drug Development

“…Current guidelines from the Centers for Disease Control and Prevention (CDC) suggest symptomatic and supportive measures as well as preventive strategies for the management of JEV infection. Control over JE suggests the important role of socio-economic parameters such as hygiene and education, but measures such as environmental manipulation, vector control, and changes in agricultural practices are difficult to achieve [ 3 , 157 , 158 ].…”

“…Various approaches are being employed to investigate potential antiviral agents against JEV infection. These include (i) a deliberate design based on the crystal structures of viral proteins; (ii) screening antiviral agent libraries approved by the FDA; (iii) the evaluation of recognised inhibitors of other human viruses; (iv) the chemical modification of viral inhibitors to enhance their therapeutic efficacy; and (v) intravenous treatment based on nucleic acids and immunoglobulins [ 55 , 158 ].…”

“…The amount of scientific literature published in recent years on JEV pathogenesis and therapeutic development is truly remarkable, and major advancements have been made in our knowledge of the pathology of JEV infection [ 3 , 14 , 19 , 35 , 55 , 158 ]. Novel therapeutic targets could offer additional opportunities for treating JE, while scientific advances in JEV research may promote treatment strategies for other flaviviruses.…”

Marine Brown Algae-Derived Compounds as Potential Inhibitors of Japanese Encephalitis Virus RNA-Dependent RNA Polymerase

“…The four natural compounds, RdRp-CMNPD16749(−15.7 Kcal/mol), RdRp-CMNPD2606 (−14.8 Kcal/mol), RdRp-CMNPD27817 (−14.4 Kcal/mol), and RdRp-CMNPD23662 (−13.9 Kcal/mol), along with the reference molecule Galidesivir, which had the −8.1 Kcal/mol binding energy, were earmarked for deeper analysis. Galidesivir is a broad-spectrum antiviral drug, effective against several RNA viruses, including families like Flaviviridae, Coronaviridae, and Filoviridae [24][25][26][27][28][29][30]. It was chosen as a reference ligand for this study due to its proven efficacy against Flaviviruses, its mechanism of action, and the valuable structural and pharmacological insights it provides.…”

Japanese encephalitis virus perturbs PML-nuclear bodies by engaging in interactions with distinct porcine PML isoforms

“…JEV encodes three structural proteins and seven nonstructural proteins (Zhu et al, 2023). To investigate the mechanism by which JEV disrupts PML-NBs, we generated overexpression vectors for JEV proteins, including Cherry-NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5, C, prM, and E. Subsequently, these 10 overexpression vectors were individually transfected into PK15 cells.…”