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

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

doi:10.1038/s41598-021-02280-5

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

Sci Rep. 2021 Nov 30;11(1):23122. doi: 10.1038/s41598-021-02280-5.

Authors

Rajani Kanta Mahato¹, Ayan Kumar Mahanty², Muddukrishnaiah Kotakonda³, Sunnapu Prasad⁴, Subires Bhattacharyya⁵, Bhaskar Biswas⁶

Affiliations

¹ Department of Chemistry, University of North Bengal, Darjeeling, 734013, India.
² Department of Biotechnology, University of North Bengal, Darjeeling, 734013, India.
³ Department of Technology, Anna University, Chennai, 600025, India.
⁴ Department of Pharmaceutical Chemistry, Sri Ramakrishna Institute of Paramedical Science, Coimbatore, 641044, India.
⁵ Vice-Chancellor, University of North Bengal, Darjeeling, 734013, India. subires.bhattacharyya@gmail.com.
⁶ Department of Chemistry, University of North Bengal, Darjeeling, 734013, India. bhaskarbiswas@nbu.ac.in.

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 (M^pro) of SARS-CoV-2. The molecular dynamics simulation studies attribute the conformationally stable structures of the DAPH⁺Cl^- bound M^pro 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Molecular Docking Simulation*
Molecular Dynamics Simulation
SARS-CoV-2*