Design of Novel Hybrid Thiourea–Phosphonate Derivatives as Potential Anti‐TMV Agents: In Silico Evaluation and (S,O)‐Pharmacophoric Site Identification

Abstract

ABSTRACT In the present study, a series of novel chiral thiourea derivatives incorporating an α‐aminophosphonate moiety were designed to target the coat protein (CP) of tobacco mosaic virus (TMV). Their potential anti‐TMV activity was further evaluated through in silico studies involving fourteen newly synthesized compounds and one reference standard. The atomic charge calculations suggested the presence of an antiviral active site (S,O‐ sp 2 ) with (S1 δ − –O1 δ − ) that was postulated from core concepts of POM theory which constitutes a reliable bioinformatics platform for the determination and optimization of the structure. Molecular docking studies were carried out to determine the binding affinities and interactions of the most potent compound 2g with the target proteins. The findings demonstrated the importance of the thiourea and aminophosphonate moieties are responsible for the superior antiviral activity and that keys Arg90 and Glu95 were important residues for TMV CP binding.