Inhibition of TNF-Alpha Using Plant-Derived Small Molecules for Treatment of Inflammation-Mediated Diseases

Abstract

Inhibition of TNF-α has become a feasible target for alleviating inflammation-mediated diseases. Currently, techniques developed, such as anti-TNF antibody therapies, prove not to be nearly as beneficial enough to effectively treat inflammation-mediated syndromes because of the increased risk for severe infections and malignancies. Our study has undertaken the attempt of identifying small molecules to inhibit TNF-α. This study manually selected 37 plant-derived compounds based on IC50 value from various literature, which showed inhibitory activity against TNF-α. By employing an in silico pipeline , we have aimed to explore the binding modes, to discover the most possible mechanism of inhibition, as well as, for a deeper understanding of structural changes, which is necessary for rationalization of the targeted inhibition by our proposed bioactive compounds. Therefore, this study has identified two potential compounds through advanced induced fit docking and simulation study. The stability of protein-ligand complex and structural changes was studied by performing 100 ns molecular dynamics simulation with its binding energy estimated through MM-PBSA analysis.

Immunomodulatory potential of bioactive compounds of betel leaf extract targeting COVID-19 immunological human host proteins: An in silico study

“…Tyr-59, Tyr-151, and Tyr-119 are active amino acids that play a crucial role in TNF-α function. By binding to this amino acid, the inhibitor can significantly impair its function (Parves et al, 2021). In addition to the active residue of tyrosine, the TNF-α binding site is composed of Leu-57, Ser-60, Gln-61, Leu-120, Gly-121, and Gly-122, so that binding to these amino acids can cause inhibition of their biological activity (He et al, 2005).…”

Potential Utilization of Phenolic Acid Compounds as Anti-Inflammatory Agents through TNF-α Convertase Inhibition Mechanisms: A Network Pharmacology, Docking, and Molecular Dynamics Approach

“…The primary objective of this study is to explore the roles of specific phenolic acid phytocompounds in healing hyperinflammation through their potential interactions with target proteins. To achieve a comprehensive understanding of their therapeutic mechanisms, a multifaceted approach was employed, integrating network pharmacology, docking studies, and molecular dynamics simulations. − …”

“…To achieve a comprehensive understanding of their therapeutic mechanisms, a multifaceted approach was employed, integrating network pharmacology, docking studies, and molecular dynamics simulations. 18 − 20 …”