AUTHOR=Tiwari Rakesh Kumar , Pandey Vinayak , Srivastava Harshita , Srivastava Ambrish Kumar , Pandey Vishnudatt 

TITLE=Docking and MM study of non-structural protein (NS5) of Japanese Encephalitis Virus (JEV) with some derivatives of adenosyl

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2023.1258764

DOI=10.3389/fchem.2023.1258764

ISSN=2296-2646

ABSTRACT=The flavivirus NS5, a non-structural protein of Japanese Encephalitis Virus (JEV), a serious deadly human pathogen responsible for epidemics in South East Asia, consists of N-terminal methyl transferase (MTase) domain and RNA-dependent RNA polymerase (RdRp) is known for unique viral genome replication and cap formation activity. Sadenosyl executes a crucial function in these viral activities. S-adenosyl derivatives are chosen as potential binders with the MTase domain of NS5 based on MM and docking studies. MM GBSA (Generalized Born Surface Area) simulation were performed to evaluate the binding energy, following the 100 nanosecond (ns) production MD simulation in the periodic boundary condition (PBC) for the selected docked ligands with NS5. Quasi-harmonic entropy of the ligands was also calculated with semiempirical calculations at the PM3/PM6 level supporting docking and MM-GBSA results.The residue-wise decomposition energy reveals that the key hydrophobic residues Gly 81, Phe 133, and Ile 147 in the RdRp-MTase interface, indicate the biological relevance.Act as the key residue stabilizer, binding with S-Adenosyl derivatives affecting vigorously, these residues, in the vicinity of the interface between MTase domain and RdRp, pave the way for the other potential drug as an inhibitor for the enzymatic activity of the NS5.