Unraveling the impact of polar solvation on the molecular geometry, spectroscopy (FT-IR, UV, NMR), reactivity (ELF, NBO, HOMO-LUMO) and antiviral inhibitory potential of Cissampeline by molecular docking approach

Cissampeline, a highly promising natural substance derived from medicinal plants of the Cissampelos genus, has recently garnered significant interest due to its potent antiviral properties against a broad spectrum of viral infections. In this comprehensive study, we employed gd3bj-B3LYP/def2svp level of theory to investigate the impact of polar solvation on the molecular structure, dynamical stability, spectroscopy, nature of bonding, and antiviral inhibitory potential of Cissampeline. Our results demonstrated excellent agreement between the theoretically characterized structure and the experimentally determined one. Interestingly, we observed that in the absence of a solvent environment, the gas phase exhibited shorter bond angles compared to when different solvents were utilized, indicating reduced solvent interactions. Regarding solvation dynamics, we found that the total energy of the structure, when optimized in different solvents, followed the order DMSO > MeOH > Water > Gas, with corresponding total final energies of 1736.599 > 867.932 > 837.760 > 413.989 kcal/mol, respectively. Furthermore, NBO analysis revealed the strength of electron delocalization, with the order of perturbation energies being DMSO > MeOH > H2O > Gas phase, measured at 626.07 > 241.40 > 238.65 > 72.93 kcal/mol, respectively. Particularly noteworthy was the σ-σ* transition in the DMSO solvent phase, displaying the highest perturbation energy of 626.07 kcal/mol. FMO analysis provided insights into the energy levels of the studied species, with values of 4.5432 eV for Gas, 4.5250 eV for MeOH, 4.5247 eV for H2O, and 4.5242 eV for DMSO, respectively. Regarding the interaction of Cissampeline with amino acid residues, we found that the ligand exhibited the highest binding affinity with 3MX2 at -7.7 kcal/mol, followed by CMPL + 3T5N at -7.3 kcal/mol, and CMPL + 3MX5 at -6.0 kcal/mol. In comparison, the standard drug RIBAV only displayed successful interaction with 3MX2, showing the least binding affinity at -5.8 kcal/mol. This study showed highlights the remarkable potential of Cissampeline as an effective antiviral agent and sheds light on the importance of considering solvation effects in molecular investigations