Repurposing immune boosting and anti-viral efficacy of
            <i>Parkia</i>
            bioactive entities as multi-target directed therapeutic approach for SARS-CoV-2: exploration of lead drugs by drug likeness, molecular docking and molecular dynamics simulation methods

Dinata, Roy; Nisa, Nisekhoto; Arati, Chettri; Rasmita, Borgohain; Uditraj, Chetia; Siddhartha, Rajkonwar; Bhanushree, Baishya; Saeed-Ahmed, Laskar; Manikandan, Bose; Bidanchi, Rema Momin; Abinash, Giri; Pori, Buragohain; Khushboo, Maurya; Roy, Vikas Kumar; Gurusubramanian, Guruswami

doi:10.1080/07391102.2023.2192797

Cited by 6 publications

(4 citation statements)

References 159 publications

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“…Previous biochemical and in silico studies have revealed that some NPs, including bile acids like tauro-α-muricholic acid 20 , 25 , β-amyrin 40 , folic acid 41 , vitamin B6 42 , campesterol and stigmasterol 43 can bind to R1, R2, or at the interface of R1–R2 interfering with the interactions between the RBD and the ACE2 receptor. These natural products thus, are proposed to have therapeutic benefits.…”

Section: Resultsmentioning

confidence: 99%

Multi-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells

Da,

Wu-Lu,

Dragelj

et al. 2023

Sci Rep

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New variants of SARS-CoV-2 that can escape immune response continue to emerge. Consequently, there is an urgent demand to design small molecule therapeutics inhibiting viral entry to host cells to reduce infectivity rate. Despite numerous in silico and in situ studies, the structural requirement of designing viral-entry inhibitors effective against multiple variants of SARS-CoV-2 has yet to be described. Here we systematically screened the binding of various natural products (NPs) to six different SARS-CoV-2 receptor-binding domain (RBD) structures. We demonstrate that Multi-structural Molecular Docking (MOD) combined with molecular dynamics calculations allowed us to predict a vulnerable site of RBD and the structural requirement of ligands binding to this vulnerable site. We expect that our findings lay the foundation for in silico screening and identification of lead molecules to guide drug discovery into designing new broad-spectrum lead molecules to counter the threat of future variants of SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Multi-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells

Da,

Wu-Lu,

Dragelj

et al. 2023

Sci Rep

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show abstract

“…CARM1 inhibition was shown to limit H3R17 methylation, resulting in decreased H3K9 acetylation and HDAC9 dissociation [268]. Ellagic acid and other plant-derived substances strongly bound with the multiple targets of the SARS-CoV-2 receptors, inhibiting viral entry, attachment, binding, replication, transcription, maturation, packaging, and spread [269]. Curcumin is known to strongly stop the production of several proinflammatory cytokines that cause the "cytokine storm" that occurs in some viral infections.…”

Section: Ellagic Acidmentioning

confidence: 99%

“…Decreases H3K9 acetylation and HDAC9 dissociation [268]. Inhibits SARS-CoV-2 viral entry and replication [269].…”

Section: Ellagic Acidmentioning

confidence: 99%

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Plant-Derived Epi-Nutraceuticals as Potential Broad-Spectrum Anti-Viral Agents

Gabbianelli,

Shahar,

de Simone

et al. 2023

Nutrients

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Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to their inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances in which vaccination is not accessible or in individuals with compromised immune systems, drugs can provide additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Moreover, targeting host factors allows us to develop compounds that are effective against different viral variants as well as against newly emerging virus strains. In recent years, the globe has experienced climate change, which may contribute to the emergence and spread of infectious diseases through a variety of factors. Warmer temperatures and changing precipitation patterns can increase the geographic range of disease-carrying vectors, increasing the risk of diseases spreading to new areas. Climate change may also affect vector behavior, leading to a longer breeding season and more breeding sites for disease vectors. Climate change may also disrupt ecosystems, bringing humans closer to wildlife that transmits zoonotic diseases. All the above factors may accelerate the emergence of new viral epidemics. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds, including those with anti-viral activity. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Interest in herbal antiviral products has increased. More than 50% of approved drugs originate from herbal sources. Plant-derived compounds offer diverse structures and bioactive molecules that are candidates for new drug development. Combining these therapies with conventional drugs could improve patient outcomes. Epigenetics modifications in the genome can affect gene expression without altering DNA sequences. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses recruit cellular epitranscriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells’ epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we explore the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing their modulation processes and anti-viral effects on DNA and RNA viruses, as well as addressing future research objectives in this rapidly emerging field.

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Based on Virtual Screening and Simulation Exploring the Mechanism of Plant-Derived Compounds with PINK1 to Postherpetic Neuralgia

Guo,

Zhang,

Liu

et al. 2024

Mol Neurobiol

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Recent studies have found that PINK1 mutation can mediate the dysfunction of mitochondrial autophagy in dopaminergic neurons; In order to reveal the role of PINK1 in the pathogenesis of PHN and nd new targets for PHN treatment. Purpose: Herein, we have employed a rigorous literature review pipeline to enlist 2801compounds from more than 200 plants from the Asian region. The virtual screening procedure helps us to shortlist the total compounds into 20 based on their better binding energy. Moreover, the Prime MM-GBSA procedure screened the compound data-set further, where Vitexin, Luteoloside, and 2'-Deoxyadenosine-5'-monophosphate had a score of (−59.439, −52.421 and − 47.544) kcal/mol, respectively. Finally, the immunohistochemistry and transmission electron microscopy (TEM) were conducted to verify the effective mechanism. The results of Immunohistochemical analysis showed that the rst two compounds had notable therapeutic effects on PHN mice, while compound 3 had no signi cant therapeutic effect. Meanwhile, the TEM result indicated that Vitexin showed the most signi cant microstructural adjustment on mitochondria. We concluded that Vitexin could alleviate PHN by regulating mitochondrial autophagy through PINK1. In this study, we observed the level of autophagy of mitochondria and the expression of PINK1 in dorsal horn neurons of PHN.

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Repurposing immune boosting and anti-viral efficacy of Parkia bioactive entities as multi-target directed therapeutic approach for SARS-CoV-2: exploration of lead drugs by drug likeness, molecular docking and molecular dynamics simulation methods

Cited by 6 publications

References 159 publications

Multi-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells

Multi-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells

Plant-Derived Epi-Nutraceuticals as Potential Broad-Spectrum Anti-Viral Agents

Based on Virtual Screening and Simulation Exploring the Mechanism of Plant-Derived Compounds with PINK1 to Postherpetic Neuralgia

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