In silico prediction of phytoconstituents from Ehretia laevis targeting TNF-α in arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease involving the synovial lining of the major joints. Current therapies have noteworthy side effects. Our study involved in silico evaluation of Ehretia laevis (E. laevis) phytoconstituents targeting tumor necrosis factor-α (TNF-α). Molecular docking studies performed to investigate the binding pattern of the plant E. laevis phytoconstituents along with the crystal structure of TNF-α (PDB ID: 2AZ5) using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents. Further the pharmacokinetic profile and toxicity screening carried out using SwissADME and pkCSM. The docked results suggest that lupeol (− 9.4 kcal/mol) and α-amyrin (− 9.4 kcal/mol) has best affinity towards TNF-α compared to standard drug thalidomide (− 7.4 kcal/mol). The active chemical constituents represents better interaction with the conserved catalytic residues, leading to the inhibition/blockade of the TNF-α-associated signaling pathway in RA. Furthermore, pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies. The binding potential of phytoconstituents targeting TNF-α showed promising results. Nonetheless, it encourages the traditional use of E. laevis and provides vital information on drug development and clinical treatment.