Adenosyl derivatives as a potential inhibitors of NS3 protease of Japanese encephalitis virus (JEV): In silico molecular insight into therapeutic discovery

The genus Flavivirus NS3 a non-structural protein of Japanes Encephalitis Virus (JEV), a serious deadly human pathogen responsible for several deaths in South East Asia, consists of helicase/NTPase domain forming a cleft known for their role in the enzymatic activity and viral replication represented biological relevance. S-Adenosyl derivatives act as powerful inhibitors in viral replication in NS5 of the same genus as of NS3, provide a powerful base to test its effectiveness in NS3 protein due to the compatibility of both proteins. The MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) simulation were performed to evaluate the binding free energy, following the 100 (ns) production MD simulation in the periodic boundary condition (PBC) for the selected docked inhibitors with NS3. The residue-wise decomposition energy determined in our study revealed the active site region made the high stability with the potential inhibitors.