Exploration of inhibitory action of Azo imidazole derivatives against COVID-19 main protease (Mpro): A computational study

Chhetri, Abhijit; Chettri, Sailesh; Rai, Pranesh; Sinha, Biswajit; Brahman, Dhiraj

doi:10.1016/j.molstruc.2020.129178

Cited by 24 publications

(28 citation statements)

References 77 publications

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“…The host nuclear import system can be bound and sequestered by pathogens such as SARS-CoV-2 allowing transportation of viral proteins to the host nucleus leading to increased viral replication [ [12] , [13] , [14] , [15] ]. Additionally, we also consider the multi-functional helicase (nsp13) of SARS-CoV-2 responsible for viral replication (PDB: 6ZSL ) [ [16] , [17] , [18] ], and the main protease (Mpro) of SARS-CoV-2 (PDB: 6LU7 ) as it is a key enzyme of coronaviruses and has a fundamental role in mediating viral replication and transcription, making it an attractive target for drugs [ 11 , [19] , [20] , [21] , [22] ]. All structures were obtained in PDB format from the RCSB protein database ( https://www.rcsb.org/ ).…”

Section: Methodsmentioning

confidence: 99%

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

González

Hurtado-León

Lossada

et al. 2021

Biophysical Chemistry

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The SARS-CoV-2 pandemic has accelerated the study of existing drugs. The mixture of homologs called ivermectin (avermectin-B1a [HB1a] + avermectin-B1b [HB1b]) has shown antiviral activity against SARS-CoV-2 in vitro . However, there are few reports on the behavior of each homolog. We investigated the interaction of each homolog with promising targets of interest associated with SARS-CoV-2 infection from a biophysical and computational-chemistry perspective using docking and molecular dynamics. We observed a differential behavior for each homolog, with an affinity of HB1b for viral structures, and of HB1a for host structures considered. The induced disturbances were differential and influenced by the hydrophobicity of each homolog and of the binding pockets. We present the first comparative analysis of the potential theoretical inhibitory effect of both avermectins on biomolecules associated with COVID-19, and suggest that ivermectin through its homologs, has a multiobjective behavior.

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Section: Methodsmentioning

confidence: 99%

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

González

Hurtado-León

Lossada

et al. 2021

Biophysical Chemistry

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“…The host nuclear import system can be bound and sequestered by pathogens such as SARS-CoV-2 allowing transportation of viral proteins to the host nucleus leading to increased viral replication [25] , [26] , [27] , [28] , [29] . Additionally, we also consider the multi-functional helicase (nsp13) of SARS-CoV-2 responsible for viral replication (PDB: 6ZSL) [30] , [31] , [32] , and the main protease (Mpro) of SARS-CoV-2 (PDB: 6LU7) as it is a key enzyme of coronaviruses and has a fundamental role in mediating viral replication and transcription, making it an attractive target for drugs [33] , [34] , [35] , [36] , [37] . All structures were obtained in PDB format from the RCSB Protein Data Bank ( https://www.rcsb.org/ ).…”

Section: Methodsmentioning

confidence: 99%

Structural deformability induced in proteins of potential interest associated with COVID-19 by binding of homologues present in ivermectin: Comparative study based in elastic networks models

González

Hurtado-León

Lossada

et al. 2021

Journal of Molecular Liquids

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The COVID-19 pandemic has accelerated the study of the potential of multi-target drugs (MTDs). The mixture of homologues called ivermectin (avermectin-B1a + avermectin-B1b) has been shown to be a MTD with potential antiviral activity against SARS-CoV-2 in vitro . However, there are few reports on the effect of each homologue on the flexibility and stiffness of proteins associated with COVID-19, described as ivermectin targets. We observed that each homologue was stably bound to identified proteinsthe proteins studied and were able to induce detectable changes with Elastic Network Models (ENMs). The perturbations induced by each homologue were characteristic of each compound and, in turn, were represented by a disruption of native intramolecular networks (interactions between residues). The homologues were able to slightly modify the conformation and stability of the connection points between the Cα atoms of the residues that make up the structural network of proteins (nodes), compared to free proteins. Each homologue was able to modified differently the distribution of quasi-rigid regions of the proteins, which could theoretically alter their biological activities. These results could provide a biophysical-computational view of the potential MTD mechanism that has been reported for ivermectin.

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“…Among the synthetic coumarin analogs, two compounds (5,6) revealed good binding energy inhibition potential. A recent work on the inhibitory action of azo-imidazole derivatives against SARS-CoV-2 M pro presented four new synthesized compounds (7-10) as promising agents by comparing the efficacy of the molecules with FDA-approved and some repurposed antiviral drugs using molecular docking and ADME research [279]. Ahmed et al synthesized three new Schiff bases as potential SARS-CoV-2 3CL pro inhibitors [280].…”

Section: Synthesis Of New Molecular Structures Against Covid-19mentioning

confidence: 99%

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

Ertürk

Şahin

et al. 2021

Molecules

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Since December 2019, humanity has faced an important global threat. Many studies have been published on the origin, structure, and mechanism of action of the SARS-CoV-2 virus and the treatment of its disease. The priority of scientists all over the world has been to direct their time to research this subject. In this review, we highlight chemical studies and therapeutic approaches to overcome COVID-19 with seven different sections. These sections are the structure and mechanism of action of SARS-CoV-2, immunotherapy and vaccine, computer-aided drug design, repurposing therapeutics for COVID-19, synthesis of new molecular structures against COVID-19, food safety/security and functional food components, and potential natural products against COVID-19. In this work, we aimed to screen all the newly synthesized compounds, repurposing chemicals covering antiviral, anti-inflammatory, antibacterial, antiparasitic, anticancer, antipsychotic, and antihistamine compounds against COVID-19. We also highlight computer-aided approaches to develop an anti-COVID-19 molecule. We explain that some phytochemicals and dietary supplements have been identified as antiviral bioproducts, which have almost been successfully tested against COVID-19. In addition, we present immunotherapy types, targets, immunotherapy and inflammation/mutations of the virus, immune response, and vaccine issues.

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Exploration of inhibitory action of Azo imidazole derivatives against COVID-19 main protease (Mpro): A computational study

Cited by 24 publications

References 77 publications

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

Structural deformability induced in proteins of potential interest associated with COVID-19 by binding of homologues present in ivermectin: Comparative study based in elastic networks models

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

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