Virtual screening, molecular dynamics simulations, and antiviral evaluation of Ocimum basilicum phytoconstituents...

In conventional medicinal systems, Ocimum basilicum (OB) is known to be effective against viral infections. A thorough screening of OB's phytoconstituents against Japanese encephalitis virus (JEV) in an in silico and in vitro model has not been documented. Therefore, we used Schrödinger software to do a virtual screening and molecular dynamics simulation (MDS) (100 ns) on 265 phytocompounds from OB against the envelope (E) protein (PDB ID: 3P54) of JEV. Chicoric acid (CA), rutin, and salvianolic acid A (SAA) complexes with the E protein showed outstanding docking scores of -9.136, -9.135, and - 11.838 (kcal/mol), which were all higher than that obtained with the reference compound mycophenolate (-4.481) (kcal/mol). MDS analysis revealed that these compounds, especially CA and rutin, showed comparatively strong stability in the binding pocket of the protein. CA and rutin also exhibited lower binding free energy with this protein than the standard. Moreover, principal component and free energy landscape analysis highlighted the antiviral potential of these compounds against JEV. In vitro experiments demonstrated the antiviral potential of CA and rutin at the early stage of the viral life cycle. These drugs also reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and reactive oxygen species in JEV-infected cells. This study provides insight into the therapeutic potential of CA and rutin as novel drugs against JEV. Additional study is needed to validate their antiviral and neuroprotective activity in an in vivo model of JE.