A hydrated 2,3-diaminophenazinium chloride as a promising building block against SARS-CoV-2

Rajani Kanta Mahato,Subires Bhattacharyya,Muddukrishnaiah Kotakonda,Ayan Kumar Mahanty,Sunnapu Prasad,Bhaskar Biswas

doi:10.1038/s41598-021-02280-5

Abstract

Phenazine scaffolds are the versatile secondary metabolites of bacterial origin. It functions in the biological control of plant pathogens and contributes to the producing strains ecological fitness and pathogenicity. In the light of the excellent therapeutic properties of phenazine, we have synthesized a hydrated 2,3-diaminophenazinium chloride (DAPH+Cl−·3H2O) through direct catalytic oxidation of o-phenylenediamine with an iron(III) complex, [Fe(1,10-phenanthroline)2Cl2]NO3 in ethanol under aerobic condition. The crystal structure, molecular complexity and supramolecular aspects of DAPH+Cl− were confirmed and elucidated with different spectroscopic methods and single crystal X-ray structural analysis. Crystal engineering study on DAPH+Cl− exhibits a fascinating formation of (H2O)2…Cl−…(H2O) cluster and energy framework analysis of defines the role of chloride ions in the stabilization of DAPH+Cl−. The bactericidal efficiency of the compound has been testified against few clinical bacteria like Streptococcus pneumoniae, Escherichia coli, K. pneumoniae using the disc diffusion method and the results of high inhibition zone suggest its excellent antibacterial properties. The phenazinium chloride exhibits a significant percentage of cell viability and a considerable inhibition property against SARS-CoV-2 at non-cytotoxic concentration compared to remdesivir. Molecular docking studies estimate a good binding propensity of DAPH+Cl− with non-structural proteins (nsp2 and nsp7-nsp-8) and the main protease (Mpro) of SARS-CoV-2. The molecular dynamics simulation studies attribute the conformationally stable structures of the DAPH+Cl− bound Mpro and nsp2, nsp7-nsp8 complexes as evident from the considerable binding energy values, − 19.2 ± 0.3, − 25.7 ± 0.1, and − 24.5 ± 0.7 kcal/mol, respectively.

Highlights

Phenazine scaffolds are the versatile secondary metabolites of bacterial origin
The DAPH+Cl− compound was synthesized through a direct catalytic oxidative coupling of o-phenylenediamine with ethanol’s previously reported mononuclear iron(III) complex
It is noticeable that the –NH and –OH stretching frequencies get merged in that region

Summary

Introduction

Phenazine scaffolds are the versatile secondary metabolites of bacterial origin. It functions in the biological control of plant pathogens and contributes to the producing strains ecological fitness and pathogenicity. The relentless outbreak of the novel coronavirus infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shatters human life and health to a severe extent throughout the w orld[1]. The clinical manifestations of COVID-19 suggest that the disease spreads through respiratory droplets of the infected individuals and leads to life-threatening conditions, including invasive lesions in the lungs leading to a serious threat to human civilizations and the living w orld[8,9,10,11,12]. Scientific literature suggests that phenazine is an important class of natural products found in nature. This redox-active nitrogen-containing heterocyclic pigment balances the redox activities inside their p roducers[32,33]

Methods

Results

Conclusion