ABSTRACT
Background. The rapidly developing resistance of viruses to synthetic antiviral drugs indicates the need to use substances with multitarget action (to avoid polypharmacy and to improve the safety of treatment). Objective(s): systematic analysis of the scientific literature on the pharmacology of bioflavonoids with an emphasis on their antiviral action. Material and methods. More than 150,000 references of primary sources were found in the PubMed/MEDLINE database of biomedical publications, including 3282 references on the antiviral effects of bioflavonoids. A systematic computerized analysis of this array of publications was carried out in order to identify the main directions in the pharmacology of bioflavonoids with an emphasis on their antiviral, antibacterial and immunomodulatory effects. The literature analysis was carried out using modern methods of topological and metric analysis of big data. Results. The molecular mechanisms of action of baicalin, hesperidin, rutin, quercetin, leukodelphinidin bioflavonoids and epigallocatechin-3gallate, curcumin polyphenols, their anti-inflammatory, antioxidant, antiviral, bactericidal, angioprotective, regenerative effects, and their prospects in therapy, prevention and rehabilitation of patients with COVID-19 and other respiratory viral infections were described in detail. Conclusion. Bioflavonoids and synergistic polyphenols exhibit not only multitarget antiviral effects by inhibiting the main protease, spike proteins, and other target proteins, but also pronounced anti-inflammatory, hepatoprotective, and immunomodulatory effects.Copyright © 2023 Modern Medical Technology. All rights reserved.
ABSTRACT
Coronavirus disease 2019 (COVID-19), named by WHO, is a real public health disaster of the third millennium. This highly contagious viral disease has infected the world population and is now a global pandemic. This acute respiratory distress syndrome (ARDS) has severe complica-tions like pneumonitis, respiratory failure, shock, multiorgan failure, and death. Well-defined FDA-approved synthetic is not yet available. Case management strategies like lockdown, use of masks and sanitizers, social distancing, and repurposing of antiviral drugs were initially undertaken to cope with this pandemic. Different broad-spectrum antiviral drugs are being repurposed as one of the treatment modalities. The global vaccination programme with the newly launched COVID-19 vac-cines, Covishield, covaxin, sputnik V, etc., is an ongoing process. Simultaneously, significant research is being carried out in search of natural antivirals and evaluating the potency of food bioac-tives to aid naturistic protection against the coronavirus. This mini-review has compiled the latest updates on the screening and evidence-based mechanistic evaluation of phytochemicals and food bioactives as non-pharmacological adjuvant aid in COVID pandemics.Copyright © 2023 Bentham Science Publishers.
ABSTRACT
Background: The recent reemergence of the coronavirus (COVID-19) caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted the search for effective treatments in the forms of drugs and vaccines. Aim(s): In this regard, we performed an in silico study on 39 active antidiabetic compounds of medicinal plants to provide insight into their possible inhibitory potentials against SARS-CoV-2 replications and post-translational modifications. Top 12 active antidiabetic compounds with potential for dual inhibition of the replications and post-translational modifications of SARS-CoV-2 were ana-lyzed. Result(s): Boswellic acids, celastrol, rutin, sanguinarine, silymarin, and withanolides expressed binding energy for 3-chymotrypsin-like protease (3CLpro) (-8.0 to-8.9 Kcal/mol), papain-like protease (PLpro) (-9.1 to-10.2 Kcal/mol), and RNA-dependent RNA polymerase (RdRp) (-8.5 to-9.1 Kcal/-mol) which were higher than the reference drugs (Lopinavir and Remdesivir) used in this study. Sanguinarine, silymarin, and withanolides are the most druggable phytochemicals among other phy-tochemicals as they follow Lipinski's rule of five analyses. Sanguinarine, silymarin, and withano-lides expressed moderate solubility with no hepatotoxicity, while silymarin and withanolides could not permeate the blood-brain barrier and showed no Salmonella typhimurium reverse mutation as-say (AMES) toxicity, unlike sanguinarine from the predictive absorption, distribution, metabolism, elimination, and toxicity (ADMET) studies. Conclusion(s): Sanguinarine, silymarin, and withanolides could be proposed for further experimental studies for their development as possible phytotherapy for the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.
ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected around 13 million people and has caused more than 5.7 lakh deaths worldwide since December 2019. In the absence of FDA approved drugs for its treatment, only symptomatic management is done. Method(s): We attempted to uncover potential therapeutic targets of spike, helicase, and RNA dependent RNA polymerase (RdRp) proteins of the SARS-CoV-2 employing a computational approach. The PDB structure of spike and RdRp and predicted structure of helicase proteins were docked with 100 approved anti-viral drugs, natural compounds, and some other chemical compounds. Result(s): The anti-SARS ligands EK1 and CID 23631927, and NCGC00029283 are potential entry in-hibitors as they showed affinity with immunogenic Receptor Binding Domain (RBD) of the spike pro-tein. This RBD interacts with Angiotensin Converting Enzyme (ACE2) receptor, facilitating the entry of virion in the host cells. The FDA approved drugs, including Nelfinavir, Saquinavir, Tipranavir, Setrobu-vir, Indinavir, and Atazanavir, showed potential inhibitory activity against targeted domains and thus, may act as entry or replication inhibitor or both. Furthermore, several anti-HCoV natural compounds, including Amentoflavone, Rutin, and Tannin, are also potential entry and replication inhibitors as they showed affinity with RBD, P-loop containing nucleoside triphosphate hydrolase, and the catalytic domain of the respective protein. Dithymoquinone showed significant inhibitory potential against the fusion peptide of S2 domain. Importantly, Tannin, Dithymoquinone, and Rutin can be extracted from Nig-ella sativa seeds and thus, may prove to be one of the most potential anti-SARS-CoV-2 inhibitors. Conclusion(s): Several potential ligands were identified with already known anti-HCoVs activities. Fur-thermore, as this study showed that some of the ligands acted as both entry and replication inhibitors against SARS-CoV-2, it is envisaged that a combination of either inhibitor with a dual mode of action would prove to be a much desired therapeutic option against this viral infection.Copyright © 2021 Bentham Science Publishers.
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The essential and fatty oils were investigated and a quantitative analysis of the root, green and stem parts of F. Longipedunculata was performed by GC-MS and HPLC-TOF/MS and their antioxidant (DPPH method) activities and potential binding of phytochemicals against SARS-CoV-2 nucleocapsid were determined using Molegro Virtual Docker software. In the root part of the plant, the prominent components of oil were beta-phellandrene (53.46%), ocimene (6.79%), 4-terpineol (5.94%) and santalol (5.03%). According to the quantitative results, vanillic acid (141.35 mg/kg), ferulic acid (126.19 mg/kg) and 4-hydroxybenzoic acid (119.92 mg/kg) were found in the roots;quercetin-3-beta-O-glycoside (1737.70 mg/kg), quercetin (531.35 mg/kg) and ferulic acid (246.22 mg/kg) were found in the in the green part;and fumaric acid (2100.21 mg/kg), quercetin-3-beta-O-glycoside (163.24 mg/kg), vanillic acid (57.59 mg/kg) were detected in the stem part. The antioxidant activity of all parts of the plant was higher than the control with BHT. Silibinin, rutin, and neohesperidin exhibited a stronger affinity than nucleotides. In the silico analysis, many of the phytochemicals were attached with strong hydrogen-bonds and electrostatic effects to the amino acids to which nucleotides are bound. The results indicated that the plant showed antioxidant effects and can be effective against SARS-CoV-2 thanks to the different phytochemical compounds it contains.
ABSTRACT
To analyze the possible mechanism of the intervention of absorbed components of Lianhua Qingwen Capsule on COVID-19 from the perspective of cytokine storm based on network pharmacology and molecular docking. Through literature mining, the components of Lianhua Qingwen capsules into blood were determined, and the related action targets of the components were searched by TCMSP and BATMAN-TCM databases. The related targets of COVID-19 and cytokine storm were screened by GeneCards, OMIM and Drugbank databases. The protein interaction PPI network was constructed through String database. DAVID database was used for GO analysis and KEGG pathway analysis. Cytoscape 3.8.0 software was used to build the network diagram. Molecular docking was performed by AutoDock software.In addition, multiple organ tissue injury, immune injury and SARS related targets were retrieved and intersected with cytokine storm.A total of 17 absorbed components of Lianhua Qingwen Capsules were collected, 237 corresponding targets and 47 targets intersected with diseases obtained, and 22 core targets screened out.GO analysis and KEGG pathway analysis presented 174 entries and 83 entries respectively (P < 0.01). The molecular docking results showed that the compounds of Emodin, Formononetin, Rutin, Gallic acid, Liquiritigenin had good binding ability with the core target of AKT1, IL-6, TP53, JUN, TNF. The proportion of intersecting target of Lianhua Qingwen Capsule and multiple organ tissue injury and immune injury was 1.6%-2.0%, and the proportion of intersecting target and SARS was 4.3%. Absorbed components of Lianhua Qingwen Capsule could effectively prevent and treat COVID-19 by intervening cytokine storm through multi-component, multi-target and multi-pathway synergistic action, and its mechanism may be related to antigen-scavenging, immune-regulating and tissue and organ protection.
ABSTRACT
BACKGROUND: Cytokine storm in COVID-19 patients has contributed to many morbidities and mortalities in patients. Studies have found that toll-like receptors (TLRs) and some Fc receptors play essential roles in the hyperactivation of the immune system. Up to date, researchers are still in progress to discover effective and safe drugs to alleviate the hyperinflammatory state in COVID-19. The previous studies had shown that Carthamus tinctorius and its bioactive compounds might have anti-inflammatory activities in animal models. AIM: We aimed to investigate the possible interactions of several flavonoids from C. tinctorius with several immune system components using a biocomputational approach. METHODS: Molecular docking was done using the AutoDock program based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) COVID-19 pathway. The most suitable receptors found were studied to study the interactions with several flavonoids from C. tinctorius. RESULTS: TLR4, TLR8, and FcγRIIa were found to bind with SARS CoV2 inflammatory pathway and further selected as macromolecules for potential interactions study with 22 flavonoids from C. tinctorius. Of the 22 flavonoids studied, daphnoretin showed the best binding affinity with TLR4 and Rutin was shown to attach best with FcγRIIa. Unlike its excellent binding to TLR4, daphnoretin showed weak binding to TLR8. CONCLUSION: Daphnoretin showed an excellent affinity with TLR4 and might be a good candidate as an inhibitor in hyperinflammatory reactions in COVID-19 DTLR8.