Table 4.

Preclinically validated molecules inhibiting JEV infections.

S. No.	Nature-Derived Compounds	Mechanisms	References
1	Arctigenin	Decreases JEV-induced neuronal apoptosis, microglial activation, and caspase activity.	[142]
2	Baicalein	Extracellular virucidal activity.	[145]
3	Cilnidipine	Inhibits JEV in high-throughput screening assay (HTS) with EC50 of 6.52 µM.	[155]
4	Cinaroside	Inhibits non-structural protein (RdRp) in silico.	[129]
5	Digoxin	Reported to act as an inhibitor of the Na+/K+-ATPase pump.	[146]
6	Echinacin	Inhibits RdRp in silico.	[129]
7	Echinacoside	Inhibits RdRp in silico.	[129]
8	FGIM-1-27	Inhibits JEV in high-throughput screening assay (HTS) with EC50 s of 3.21 µM.	[155]
9	Gedunin	Inhibits RdRp in silico.	[154]
10	Genistein	Reduces the effect of neurotoxicity induced by JEV and suppresses the cachectin (TNF-α) and leukocytic pyrogen (IL-1β) prompted by JEV at the transcriptional level.	[149]
11	Herbimycin A	Reduces the effect of neurotoxicity induced by JEV and suppresses the cachectin (TNF-α) and leukocytic pyrogen (IL-1β) prompted by JEV at the transcriptional level.	[149]
12	IFIT 1	Inhibits JEV replication by binding to the 5′ -triphosphate RNA and, most preferably, to the 5′ capped 2′-O unmethylated mRNA.	[150]
13	Kaempferol-3-glucoside	Inhibits RdRp in silico.	[129]
14	Kulactone	Inhibits RdRp in silico.	[154]
15	Manidipine	Inhibits intracellular Ca2+, which is required for JEV entry, replication, and budding.	[149]
16	Mycophenolic acid	Reported antiviral activity of an immune suppressant as an anti-JEV drug via plaque reduction neutralization assay, virus yield reduction assay, and cytopathic effect inhibition assay, accompanied by an IC50 of 3.1 µg/mL through in vivo and in vitro experiments.	[156]
17	Niclosamide	Inhibits JEV with EC50 of 5.80 µM	[155]
18	Nimbolide	Inhibits RdRp in silico.	[154]
19	Nitazoxanide	Inhibits the replication machinery, validated through both in vivo as well as in vitro methods, which suggests this compound is a potential agent for JE treatment.	[152,157]
20	Ohchinin acetate	Inhibits non-structural protein (RdRp) in silico.	[154]
21	Ouabain	Reported against the Na+/K+-ATPase as an inhibitor during the replication of the JEV in the BALB/C mouse model	[147]
22	PP2	Reduces the effect of neurotoxicity induced by JEV and suppresses the Cachectin (TNF-α) and leukocytic pyrogen (IL-1β) prompted by JEV at the transcriptional level.	[149]
23	Quercetagetin 7-glucoside	Inhibits RdRp in silico.	[129]
24	Rosmarinic acid	Reduces induction of proinflammatory mediators, neuronal apoptosis, microglial activation, and caspase activation.	[143]
25	Rutin	Inhibits RdRp in silico.	[129]
26	TRIM52	NS2A was degraded by TRIM 52 within a proteosome-dependent process through E3 Ubiquitin synthetase activity. Overexpression of TRIM52 in BHK-21 cells directly shows E3 Ubiquitin ligase activity and activation of the host innate immune system.	[151]