Role of inflammatory cytokine burst in neuro-invasion of Japanese Encephalitis virus infection: an immunotherapeutic approaches.

Japanese Encephalitis remains a significant global health concern, contributing to millions of deaths annually worldwide. Microglial cells, as key innate immune cells within the central nervous system (CNS), exhibit intricate cellular structures and possess molecular phenotypic plasticity, playing pivotal roles in immune responses during CNS viral infections. Particularly under viral inflammatory conditions, microglial cells orchestrate innate and adaptive immune responses to mitigate viral invasion and dampen inflammatory reactions. This review article comprehensively summarizes the pathophysiology of viral invasion into the CNS and the cellular interactions involved, elucidating the roles of various immune mediators, including pro-inflammatory cytokines, in neuroinflammation. Leveraging this knowledge, strategies for modulating inflammatory responses and attenuating hyperactivation of glial cells to mitigate viral replication within the brain are discussed. Furthermore, current chemotherapeutic and antiviral drugs are examined, elucidating their mechanisms of action against viral replication. This review aims to provide insights into therapeutic interventions for Japanese Encephalitis and related viral infections, ultimately contributing to improved outcomes for affected individuals.

Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study.

Mycobacterium tuberculosis (M.tb.) enoyl-acyl carrier protein (ACP) reductase (InhA) is validated as a useful target for tuberculosis therapy and is considered an attractive enzyme to drug discovery. This study aimed to identify the novel inhibitor of the InhA enzyme, a potential target of M.tb. involved in the type II fatty acid biosynthesis pathway that controls mycobacterial cell envelope synthesis. We compiled 80 active compounds from Ruta graveolens and citrus plants belonging to the Rutaceae family for pharmacokinetics and molecular docking analyses. The chemical structures of the 80 phytochemicals and the 3D structure of the target protein were retrieved from the PubChem database and RCSB Protein Data Bank, respectively. The evaluation of druglikeness was performed based on Lipinski's Rule of Five, while the computed phytochemical properties and molecular descriptors were used to predict the ADMET of the compounds. Amongst these, 11 pharmacokinetically-screened compounds were further examined by performing molecular docking analysis with an InhA target using AutoDock 4.2. The docking results showed that gravacridonediol, a major glycosylated natural alkaloid from Ruta graveolens, might possess a promising inhibitory potential against InhA, with a binding energy (B.E.) of -10.80 kcal/mole and inhibition constant (Ki) of 600.24 nM. These contrast those of the known inhibitor triclosan, which has a B.E. of -6.69 kcal/mole and Ki of 12.43 µM. The binding efficiency of gravacridonediol was higher than that of the well-known inhibitor triclosan against the InhA target. The present study shows that the identified natural compound gravacridonediol possesses drug-like properties and also holds promise in inhibiting InhA, a key target enzyme of M.tb.