Molecular Docking and Dynamics Analyses for Evaluation of Interactions Between the Human Receptor and Viral Proteins of Enterovirus A71

Abstract

Enterovirus A71 (EV‐A71) is a major cause of hand, foot, and mouth disease and is linked to severe neurological complications in children. No approved antiviral therapy is currently available, and vaccine coverage remains limited, highlighting the need for new therapeutics. This study examined interactions between EV‐A71 proteins (VP0, VP1‐VP4, and 3C protease) and the human receptor SCARB2 using molecular docking and molecular dynamics (MD) simulations under balanced, electrostatic, hydrophobic, and VdW+Elec conditions. Among all complexes, SCARB2‐VP3 showed the highest stability, with hydrophobic‐favored scores of −1358.8/−1650.1 (70 members), balanced (−994.7/−1251.3; 59 members), electrostatic‐favored (−987.3/−1069.8; 69 members), and VdW+Elec (−165.0/−201.6), indicating consistently strong affinity. MD results showed that in the balanced system SCARB2‐VP3 had RMSD 1.47 ± 1.42 nm, RMSF 1.60 ± 0.72 nm, Rg 3.44 ± 0.91 nm, and 25 H‐bonds. In electrostatic conditions, it showed RMSD 3.25 ± 1.33 nm and Rg 4.61 ± 0.89 nm. Under hydrophobic mode, it remained compact (Rg 3.82 ± 0.81 nm) with 17 H‐bonds. In VdW+Elec, it showed RMSD 1.04 ± 0.70 nm, RMSF 0.92 ± 0.36 nm, and Rg 3.19 ± 0.52 nm. Cross‐docking confirmed binding to PSGL‐1 (3O2U), ICAM‐1 (1IC1), and DAF/CD55 (1H03). These findings reveal key EV‐A71–SCARB2 interaction mechanisms.