Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: Molecular Docking and DFT Calculations

Mohamed Hagar, Hoda A. Ahmed, Ghadah Aljohani, Omaima A. Alhaddad

10.3390/ijms21113922

Research curated

Abstract

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.

Source: PubMed

Related molecules

Name	Synonyms	Genes
2'-Deoxy-2'-fluorocytidine	2'-Fluoro-2'-deoxycytidine,
Ribavirin	RBV, 1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide, 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide
Amodiaquine
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Favipiravir	favilavir, Avifavir

Related interactions

Target	Drug	Type	Result
3C-like protease	Favipiravir	Computational	positive
3C-like protease	Amodiaquine	Computational	positive
3C-like protease	Ribavirin	Computational	positive
3C-like protease	2'-Deoxy-2'-fluorocytidine	Computational	positive