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

doi:10.3390/ijms21113922

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.

Highlights

Novel coronavirus (COVID-19) emerged as an infection and quickly spread to all countries and is primarily transmitted by contact with infected droplets of saliva or discharge from the nose when infected people cough or sneeze
COVID-19 is a novel coronavirus of the β genus; it is round in shape or crown-shaped and has a diameter of ≈ 60–140 nm, as per observations under the electron microscopy [3]
The results revealed that amodiaquine (2) and ribavirin (4) showed the best affinity with the target receptor, even though this behavior was not experimentally verified

Summary

Introduction

Novel coronavirus (COVID-19) emerged as an infection and quickly spread to all countries and is primarily transmitted by contact with infected droplets of saliva or discharge from the nose when infected people cough or sneeze. SARS-COV-2, the big family of COVID-19, is sensitive to heat and ultraviolet (UV) rays They are inactivated at 56 ◦C for half hour and can be stored at −80 ◦C for many years. There are no SARS-CoV-2 vaccines available, several domestic and foreign research institutions and enterprises have used several methods, including mRNA nano-vaccine technology, recombinant or inactivated vaccine technology, and DNA vaccine technology, to develop coronavirus vaccine [5]. The treatment of this virus has not been achieved by any available antiviral agent. Our present work suggests that selection of some derivatives with the appropriate viral restraining mechanisms can offer promising results

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