Table 3.

Thermodynamic Binding Free Energy Profiles for the hit molecules and standard drugs towards COVID-19 M_pro.

Energy Components (kcal/mol)
Complex	Δ EvdW	ΔEelec	ΔGgas	ΔGsolv	ΔGbind
N3	−61.685 ± 5.383	−139.335 ± 17.103	−201.020 ± 19.795	148.556 ± 12.436	−52.463 ± 4.937
NEF	−55.881 ± 4.046	−151.517 ± 11.509	−207.399 ± 11.671	155.780 ± 9.653	−51.618 ± 4.906
RDV	−57.869 ± 3.670	−21.668 ± 5.969	−79.537 ± 6.245	30.757 ± 4.669	−48.780 ± 3.804
LPV	−62.806 ± 8.979	−19.616 ± 3.098	−82.422 ± 13.158	5.634 ± 6.298	−46.788 ± 7.840
DRV	−46.018 ± 3.040	−16.176 ± 4.849	−62.195 ± 5.640	28.539 ± 4.232	−33.655 ± 3.374
HCQ	−18.548 ± 0.381	−48.905 ± 1.240	−53.453 ± 1.596	45.388 ± 1.328	−21.065 ± 0.293
Lead Molecules
HCR	−56.0056 ± 5.126	−146.740 ± 16.786	−202.748 ± 15.220	152.870 ± 11.894	−53.877 ± 4.886
GRN	−54.3287 ± 4.186	−30.887 ± 6.205	−85.2167 ± 7.681	38.563 ± 4.326	−50.653 ± 3.140
EGCG	−36.4632 ± 4.615	−72.369 ± 10.499	−108.832 ± 9.460	62.232 ± 5.336	−48.600 ± 5.217
C3G	−48.8334 ± 5.099	−140.163 ± 20.932	−189.001 ± 20.053	143.202 ± 15.368	−47.798 ± 4.231
K7G	−45.9164 ± 4.053	−35.158 ± 12.099	−81.075 ± 10.496	37.172 ± 8.693	−46.902 ± 5.288
P3G	−37.5272 ± 3.485	−128.148 ± 14.775	−165.678 ± 15.444	133.629 ± 12.379	−32.049 ± 4.760

ΔE_ele electrostatic energy, ΔE_vdW van der Waals energy, ΔG_bind total binding free energy, ΔG_sol solvation free energy, ΔE_gas gas-phase free energy.