Chloroquine and hydroxychloroquine inhibitors for COVID-19 sialic acid cellular receptor: Structure, hirshfeld atomic charge analysis and solvent effect

Altalhi, Tariq; Alswat, Khaled; Alsanie, Walaa F.; Ibrahim, Mohamed M.; Aldalbahi, Ali; El‐Sheshtawy, Hamdy S.

doi:10.1016/j.molstruc.2020.129459

Cited by 11 publications

(6 citation statements)

References 48 publications

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“…Furthermore, recent studies have shed a light on molecular docking methodologies as powerful techniques in establishing therapeutic strategies to combat COVID-19 pandemic. In context to the recent demands, molecular docking approach has been applied for screening of organic molecules and coordination complexes as potent inhibitor of COVID-19 virus [ [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] – 35 ]. Metal complexes will eventually lead to the destruction of COVID-19 virus.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, crystal structure, computational study and anti-virus effect of mixed ligand copper (II) complex with ONS donor Schiff base and 1, 10-phenanthroline

Mohan

Choudhary

2021

Journal of Molecular Structure

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This work deals with the synthesis, crystal structure, computational study and antiviral potential of mixed ligand copper(II) complex [Cu(L)(phen)]( 1 ), (where, H 2 L = ( Z )- N ’-(( E )-2-hydroxy-3,5-diiodobenzylidene)- N,N- dimethylcarbamohydrazonothioic acid, phen = 1,10-phenanthroline). The Schiff base ligand (H 2 L) is coordinated with Cu(II) ion in O, N, S-tridentate mode. The copper complex ( 1 ) crystallized in the monoclinic system of the space group P21/c with eight molecules in the unit cell and reveals a square pyramidal geometry. Furthermore, we also perform quantum chemical calculations to get insights into the structure-property relationship and functional properties of ligand (H 2 L) and its copper (II) complex [Cu(L)(phen)]( 1 ). Complex [Cu(L)(phen)]( 1 ) was also virtually designed in-silico evaluation by Swiss-ADME. Additionally, inspiring by recent developments to find a potential inhibitor for the COVID-19 virus, we have also performed molecular docking study of ligand and its copper complex ( 1 ) to see if our compounds shows an affinity for the main protease (M pro ) of COVID-19 spike protein (PDB ID: 7C8U ). Interestingly, the results are found quite encouraging where the binding affinity and inhibition constant were found to be -7.14 kcal/mol and 5.82 μM for ligand (H 2 L) and -6.18 kcal/mol and 0.76 μM for complex [Cu(L)(phen)]( 1 ) with M pro protein. This binding affinity is reasonably well as compared to recently known antiviral drugs. For instance, the binding affinity of ligand and complex was found to be better than docking results of chloroquine (-6.293 kcal/mol), hydroxychloroquine (-5.573 kcal/mol) and remdesivir (-6.352 kcal/mol) with M pro protein. The present study may offer the technological solutions and potential inhibition to the COVID-19 virus in the ongoing and future challenges of the global community. In the framework of synthesis and characterization of mixed ligand copper (II) complex; the major conclusions can be drawn as follow:

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Section: Introductionmentioning

confidence: 99%

Synthesis, crystal structure, computational study and anti-virus effect of mixed ligand copper (II) complex with ONS donor Schiff base and 1, 10-phenanthroline

Mohan

Choudhary

2021

Journal of Molecular Structure

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“…In a study on hypertensive drugs targeting the coupling of ACE2 in the host and S protein in SARS-CoV-2, the antiviral activity of Ramipril, with higher chemical softness and electrophilicity index values, was determined to be more promising than other drugs [100]. Molecular electrostatic potential (MEP) maps are one of the tools used in the docking of ligands with SARS-CoV-2 proteins depending on their charge density to predict the regions that will provide the most appropriate geometry and score value [100][101][102]. MEP maps created with computational methods estimate sites that are especially sensitive to electrophilic and nucleophilic interactions of molecular structures before molecular docking [103][104][105].…”

Section: Computer Aided Drug Designmentioning

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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“…Among them are sialic acids, which are produced and investigated for this reason, as they are found in cell membranes and play an important role in cell adhesion and signaling [ 1 ]. They are also studied, for instance, in Covid-19 research [ 2 ]. It has been pointed out that derivatives from Neu5Ac can inhibit viral enzymes [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

Reich¹,

Aßmann²,

Hölting³

et al. 2022

Beilstein J. Org. Chem.

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The importance of a compound that helps fight against influenza is, in times of a pandemic, self-evident. In order to produce these compounds in vast quantities, many researchers consider continuous flow reactors in chemical industry as next stepping stone for large scale production. For these reasons, the synthesis of N-acetylneuraminic acid (Neu5Ac) in a continuous fixed-bed reactor by an immobilized epimerase and aldolase was investigated in detail. The immobilized enzymes showed high stability, with half-life times > 173 days under storage conditions (6 °C in buffer) and reusability over 50 recycling steps, and were characterized regarding the reaction kinetics (initial rate) and scalability (different lab scales) in a batch reactor. The reaction kinetics were studied in a continuous flow reactor. A high-pressure circular reactor (up to 130 MPa) was applied for the investigation of changes in the position of the reaction equilibrium. By this, equilibrium conversion, selectivity, and yield were increased from 57.9% to 63.9%, 81.9% to 84.7%, and 47.5% to 54.1%, respectively. This indicates a reduction in molar volume from N-acetyl-ᴅ-glucosamine (GlcNAc) and pyruvate (Pyr) to Neu5Ac. In particular, the circular reactor showed great potential to study reactions at high pressure while allowing for easy sampling. Additionally, an increase in affinity of pyruvate towards both tested enzymes was observed when high pressure was applied, as evidenced by a decrease of KI for the epimerase and KM for the aldolase from 108 to 42 mM and 91 to 37 mM, respectively.

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Chloroquine and hydroxychloroquine inhibitors for COVID-19 sialic acid cellular receptor: Structure, hirshfeld atomic charge analysis and solvent effect

Cited by 11 publications

References 48 publications

Synthesis, crystal structure, computational study and anti-virus effect of mixed ligand copper (II) complex with ONS donor Schiff base and 1, 10-phenanthroline

Synthesis, crystal structure, computational study and anti-virus effect of mixed ligand copper (II) complex with ONS donor Schiff base and 1, 10-phenanthroline

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

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