In vitro potential antiviral SARS-CoV-19- activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa

Esharkawy, Eman R.; Almalki, Faisal A.; Hadda, Taïbi Ben

doi:10.1016/j.bioorg.2021.105587

Cited by 47 publications

(25 citation statements)

References 73 publications

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“…Recently, we discovered the Dithymoquinone as potential anti-Covid-19 with MIC in range of nano-Molar [63] . Interestingly, we compare the pharmacophore site of the Dithymoquinone (dO1-O2 = 4.5 A) and the combined antibacterial/antiviral pharmacophore site of compound 4b (dO1-O2 = 4.6 A).…”

Section: Resultsmentioning

confidence: 99%

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity

Chalkha

Nakkabi

Hadda

et al. 2022

Journal of Molecular Structure

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Section: Resultsmentioning

confidence: 99%

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity

Chalkha

Nakkabi

Hadda

et al. 2022

Journal of Molecular Structure

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“…Thymoquinone (THY) is one of the major constituents (28–57%) of black seed ( N. sativa ) oil. It has different biological activities, including cytotoxic, anti-inflammatory, anti-microbial, anti-viral, anti-oxidant, immune-stimulant, and anticoagulant effects [ 43 ]. Moreover, it has the ability to reduce the levels of pro-inflammatory mediators (ILs 2, 4, 6, and 12) and increases INF-γ [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics

Abdallah

El-Halawany

Darwish

et al. 2022

Plants

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Since the emergence of the pandemic of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of antiviral phytoconstituents from medicinal plants against SARS-CoV-2 has been comprehensively researched. In this study, thirty-three plants belonging to seventeen different families used traditionally in Saudi Arabia were tested in vitro for their ability to inhibit the SARS-CoV-2 main protease (MPRO). Major constituents of the bio-active extracts were isolated and tested for their inhibition potential against this enzyme; in addition, their antiviral activity against the SARS-CoV-2 Egyptian strain was assessed. Further, the thermodynamic stability of the best active compounds was studied through focused comparative insights for the active metabolites regarding ligand–target binding characteristics at the molecular level. Additionally, the obtained computational findings provided useful directions for future drug optimization and development. The results revealed that Psiadia punctulata, Aframomum melegueta, and Nigella sativa extracts showed a high percentage of inhibition of 66.4, 58.7, and 31.5%, against SARS-CoV-2 MPRO, respectively. The major isolated constituents of these plants were identified as gardenins A and B (from P. punctulata), 6-gingerol and 6-paradol (from A. melegueta), and thymoquinone (from N. sativa). These compounds are the first to be tested invitro against SARS-CoV-2 MPRO. Among the isolated compounds, only thymoquinone (THY), gardenin A (GDA), 6-gingerol (GNG), and 6-paradol (PAD) inhibited the SARS-CoV-2 MPRO enzyme with inhibition percentages of 63.21, 73.80, 65.2, and 71.8%, respectively. In vitro assessment of SARS-CoV-2 (hCoV-19/Egypt/NRC-03/2020 (accession number on GSAID: EPI_ISL_430820) revealed a strong-to-low antiviral activity of the isolated compounds. THY showed relatively high cytotoxicity and was anti-SARS-CoV-2, while PAD demonstrated a cytotoxic effect on the tested VERO cells with a selectivity index of CC50/IC50 = 1.33 and CC50/IC50 = 0.6, respectively. Moreover, GNG had moderate activity at non-cytotoxic concentrations in vitro with a selectivity index of CC50/IC50 = 101.3/43.45 = 2.3. Meanwhile, GDA showed weak activity with a selectivity index of CC50/IC50 = 246.5/83.77 = 2.9. The thermodynamic stability of top-active compounds revealed preferential stability and SARS-CoV-2 MPRO binding affinity for PAD through molecular-docking-coupled molecular dynamics simulation. The obtained results suggest the treating potential of these plants and/or their active metabolites for COVID-19. However, further in-vivo and clinical investigations are required to establish the potential preventive and treatment effectiveness of these plants and/or their bio-active compounds in COVID-19.

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“…In addition, DTQ has shown the potential to inhibit the viral-host interaction for the SARS-CoV-2 infection [ 47 ]. Esharkawy et al [ 48 ] checked the vitro anti-SARS-CoV-2 activity of DTQ and thymohydroquinone. They found that DTQ showed an IC 50 value of 275.2 ng/mL against SARS-CoV-2-infected cells; however, it was cytotoxic against uninfected VERO-E6 cells.…”

Section: Resultsmentioning

confidence: 99%

Dithymoquinone Analogues as Potential Candidate(s) for Neurological Manifestation Associated with COVID-19: A Therapeutic Strategy for Neuro-COVID

Moin

Huwaimel

Alobaida

et al. 2022

Life

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The COVID-19 era has prompted several researchers to search for a linkage between COVID-19 and its associated neurological manifestation. Toll-like receptor 4 (TLR-4) acts as one such connecting link. spike protein of SARS-CoV-2 can bind either to ACE-2 receptors or to TLR-4 receptors, leading to aggregation of α-synuclein and neurodegeneration via the activation of various cascades in neurons. Recently, dithymoquinone has been reported as a potent multi-targeting candidate against SARS-CoV-2. Thus, in the present study, dithymoquinone and its six analogues were explored to target 3CLpro (main protease of SARS-CoV-2), TLR4 and PREP (Prolyl Oligopeptidases) by using the molecular docking and dynamics approach. Dithymoquinone (DTQ) analogues were designed in order to investigate the effect of different chemical groups on its bioactivity. It is noteworthy to mention that attention was given to the feasibility of synthesizing these analogues by a simple photo-dimerisation reaction. The DTQ analogue containing the 4-fluoroaniline moiety [Compound (4)] was selected for further analysis by molecular dynamics after screening via docking-interaction analyses. A YASARA structure tool built on the AMBER14 force field was used to analyze the 100 ns trajectory by taking 400 snapshots after every 250 ps. Moreover, RMSD, RoG, potential energy plots were successfully obtained for each interaction. Molecular docking results indicated strong interaction of compound (4) with 3CLpro, TLR4 and PREP with a binding energy of −8.5 kcal/mol, −10.8 kcal/mol and −9.5 kcal/mol, respectively, which is better than other DTQ-analogues and control compounds. In addition, compound (4) did not violate Lipinski’s rule and showed no toxicity. Moreover, molecular dynamic analyses revealed that the complex of compound (4) with target proteins was stable during the 100 ns trajectory. Overall, the results predicted that compound (4) could be developed into a potent anti-COVID agent with the ability to mitigate neurological manifestations associated with COVID-19.

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In vitro potential antiviral SARS-CoV-19- activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa

Abstract: Graphical abstract

Cited by 47 publications

References 73 publications

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity

Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics

Dithymoquinone Analogues as Potential Candidate(s) for Neurological Manifestation Associated with COVID-19: A Therapeutic Strategy for Neuro-COVID

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