Multi-Targeted Molecular Docking and Drug-Likeness Evaluation of some
Nitrogen Heterocyclic Compounds Targeting Proteins Involved in the
Development of COVID-19

Lok   Yong   Hui; Chan   Sook   Mun; Lai   Cong   Sing; Harish      Rajak; Rohini      Karunakaran; Veerasamy      Ravichandran

doi:10.2174/1573406418666220616110351

Abstract

Background: The severe acute respiratory syndrome coronavirus-2 is causing a disaster through coronavirus disease-19 (COVID-19), affecting the world population with a high mortality rate. Although numerous scientific efforts have been made, we do not have any specific drug for COVID-19 treatment.

Objective: Aim of the present study was to analyse the molecular interaction of nitrogen heterocyclic based drugs (hydroxychloroquine, remdesivir and lomefloxacin) with various SARSCoV- 2 proteins (RdRp, PLPro, Mpro and spike proteins) using a molecular docking approach.

Methods: We have performed docking study using PyRx software, and Discovery Studio Visualizer was used to visualise the molecular interactions. The designed nitrogen heterocyclic analogues were checked for Lipinski’s rule of five, Veber's Law and Adsorption, Distribution, Metabolism, and Excretion (ADME) threshold. After obtaining the docking results of existing nitrogen heterocyclic drugs, we modified the selected drugs to get molecules with better affinity against SARS-CoV-2.

Results: Hydroxychloroquine bound to RdRp, spike protein, PLPro and Mpro at -5.2, -5.1, -6.7 and -6.0 kcal/mol, while remdesivir bound to RdRp, spike protein, PLPro, and Mpro at -6.1, -6.9, -6.4 and -6.9 kcal/mol, respectively. Lomefloxacin bound to RdRp, spike protein, PLPro and Pro at -6.4, -6.6, -7.2 and -6.9 kcal/mol. ADME studies of all these compounds indicated lipophilicity and high gastro intestine absorbability. The modified drug structures possess better binding efficacy towards at least one target than their parent compounds.

Conclusion: The outcome reveals that the designed nitrogen heterocyclics could contribute to developing the potent inhibitory drug SARS-CoV-2 with strong multi-targeted inhibition ability and reactivity

Keywords: Coronavirus disease-19, nitrogen heterocyclics, molecular docking, SARS-CoV-2, multitarget, pneumonia outbreak.

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DOI https://dx.doi.org/10.2174/1573406418666220616110351	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638

Medicinal Chemistry

Multi-Targeted Molecular Docking and Drug-Likeness Evaluation of some Nitrogen Heterocyclic Compounds Targeting Proteins Involved in the Development of COVID-19

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