The novel coronavirus,
COVID-19, caused by SARS-CoV-2, is a global health pandemic that started in December 2019. The effective
drug target among coronaviruses is the main
protease Mpro, because of its essential role in processing the
polyproteins that are translated from the
viral RNA. In this study, the bioactivity of some selected heterocyclic drugs named
Favipiravir (1),
Amodiaquine (2),
2'-Fluoro-2'-deoxycytidine (3), and
Ribavirin (4) was evaluated as inhibitors and
nucleotide analogues for
COVID-19 using computational modeling strategies. The density functional theory (DFT) calculations were performed to estimate the thermal parameters, dipole moment, polarizability, and molecular electrostatic potential of the present drugs; additionally, Mulliken atomic charges of the drugs as well as the chemical reactivity descriptors were investigated. The nominated drugs were docked on
SARS-CoV-2 main protease (PDB: 6LU7) to evaluate the binding affinity of these drugs. Besides, the computations data of DFT the docking simulation studies was predicted that the
Amodiaquine (2) has the least binding energy (-7.77 Kcal/mol) and might serve as a good inhibitor to SARS-CoV-2 comparable with the approved medicines,
hydroxychloroquine, and
remdesivir which have binding affinity -6.06 and -4.96 Kcal/mol, respectively. The high binding affinity of 2 was attributed to the presence of three hydrogen bonds along with different hydrophobic interactions between the
drug and the critical
amino acids residues of the receptor. Finally, the estimated molecular electrostatic potential results by DFT were used to illustrate the molecular docking findings. The DFT calculations showed that
drug 2 has the highest of lying HOMO, electrophilicity index, basicity, and dipole moment. All these parameters could share with different extent to significantly affect the binding affinity of these drugs with the active
protein sites.