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6-paradol for COVID-19

6-paradol has been reported as potentially beneficial for COVID-19 in the following studies. We have not reviewed 6-paradol in detail.
COVID-19 involves the interplay of over 100 viral and host proteins and factors providing many therapeutic targets. Scientists have proposed over 9,000 potential treatments. c19early.org analyzes 160+ treatments.
Umar et al., Molecular docking of SARS-CoV-2 surface proteins with some active metabolites from plants used in the therapy of common cold: potential drug identifcation, Journal of Umm Al-Qura University for Applied Sciences, doi:10.1007/s43994-025-00237-2
Abstract Coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Although many vaccines have been developed against the virus, problems associated with vaccine resistance, vaccine apathy and the evolution of variants of the virus with increased transmissibility calls for the development of more effective and affordable drugs to combat the disease. Natural source drugs are regarded as an essential part of the therapy regimen for COVID-19 treatment and other viral respiratory infections as such needs to be exploited for the treatment of the virus globally. The study aimed to computationally screen the phytochemicals of some Nigerian plants used in the therapy of common cold for anti-COVID-19 activity. Phytochemical analysis of the plant extracts was performed employing standard techniques, while Gas chromatography–mass spectrometry was used to detect the bioactive compounds present in the extracts. The selected plant bioactive compounds were docked against the SARS-CoV-2 Main protease (Mpro), RNA-dependent RNA polymerase (RdRp), and S protein-ACE2 targets, while Lopinavir, Remdesivir and Favipiravir were included as standard ligands. The phytochemical constituents of the extracts were steroids, flavonoids, saponins, tannins, phenols, glycosides, terpenoids, and alkaloids. All the bioactive compounds exhibited acceptable drug-likeness and good oral bioavailability prediction, in addition to 89% of the compounds having slightly or practically non-oral toxicity using SwissADME and ProTox-II prediction servers. The overall result suggested that 3-Epimoretenol, Beta-Amyrin acetate, Methyl 3-oxours-12-en-23-oate, 20(29)-Lupenol acetate and Lanosterol acetate are the top most promising therapeutic bioactive natural compounds with antiviral activity against the SARS-CoV-2 Mpro, RdRp and spike protein when compared to standard drugs. Taken together, data obtained reveal that these bioactive natural compounds may have a very good potential as anti-COVID-19 therapy.
Abdallah et al., Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics, Plants, doi:10.3390/plants11151914
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.
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
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