Modular Approach to In Silico Antiviral Multitargets Inhibitor: Molecular Dockings, Dynamics, Principal Component Analysis, Clustering, and Energy Landscape

Abstract

ABSTRACT Antiviral multitarget inhibitory capacity of certain structural candidates against antiviral targets, M pro , PLpro, and RBD‐ACE2 interface were assessed in a modular approach. Among the structures analyzed, the compound tiliroside, present in Zygophyllum coccineum , emerged as the potent multitarget inhibitor in the molecular docking studies. Molecular dynamics simulations, performed for 100 ns in triplicate, confirmed the binding stability of the compound to M pro , PLpro, and RBD‐ACE2 interface, together with MM‐GBSA binding affinities of ∼ −93.55, −68.55, and −62.39 kcal/mol, respectively. The protein backbone RMSDs for these complexes remained within the range of ∼1.7 to 2.8 Å, indicating stable complexes. The root mean square fluctuation (RMSF) analysis, secondary structure monitoring, principal component analysis, clustering, and Gibbs free energy landscape assessments supported the stability of these complexes. Additionally, residue‐specific interaction analysis and binding energy decomposition provided insights into the key elements driving these bindings. The results underscored the potential of the tiliroside as a multitarget inhibitor of viral proteins.