Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols

Bahun, Miha; Jukič, Marko; Oblak, Domen; Kranjc, Luka; Bajc, Gregor; Butala, Matej; Bozovičar, Krištof; Bratkovič, Tomaž; Podlipnik, Črtomir; Ulrih, Nataša Poklar

doi:10.1016/j.foodchem.2021.131594

Cited by 87 publications

(85 citation statements)

References 40 publications

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“…On the other hand, potential modes of antiviral actions of Hypericum perforatum against SARS-CoV-2 were introduced, since hypericin and pseudohypericin were anticipated, by molecular docking, to form a stable complex with the main (3CL) protease or the RNA polymerase of the SARS-CoV-2 [ 62 , 63 ] or had a high affinity toward SARS-CoV-2 basic proteins [ 64 ] but with only little clarification about biological evidence so far. However, it was found that some plant polyphenols could inhibit the 3CL protease using certain experimental settings [ 65 ]. Apart from the virological studies shown and discussed here, the well-described antidepressant effect of Hypericum perforatum was indirectly linked to its ability to inhibit synaptosomal reuptake of serotonin and other biogenic amines in vitro or to modulate serotonin receptors in vivo [ 66 ], suggesting that it may affect membranes (cellular or viral) in general.…”

Section: Discussionmentioning

confidence: 99%

Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2

et al. 2022

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For almost two years, the COVID-19 pandemic has constituted a major challenge to human health, particularly due to the lack of efficient antivirals to be used against the virus during routine treatment interventions. Multiple treatment options have been investigated for their potential inhibitory effect on SARS-CoV-2. Natural products, such as plant extracts, may be a promising option, as they have shown an antiviral activity against other viruses in the past. Here, a quantified extract of Hypericum perforatum was tested and found to possess a potent antiviral activity against SARS-CoV-2. The antiviral potency of the extract could be attributed to the naphtodianthrones hypericin and pseudohypericin, in contrast to other tested ingredients of the plant material, which did not show any antiviral activity. Hypericum perforatum and its main active ingredient hypericin were also effective against different SARS-CoV-2 variants (Alpha, Beta, Delta, and Omicron). Concerning its mechanism of action, evidence was obtained that Hypericum perforatum and hypericin may hold a direct virus-blocking effect against SARS-CoV-2 virus particles. Taken together, the presented data clearly emphasize the promising antiviral activity of Hypericum perforatum and its active ingredients against SARS-CoV-2 infections.

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Section: Discussionmentioning

confidence: 99%

Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2

et al. 2022

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“…A number of recent review papers, and some experimental works, suggest that the use of dietary bioactive compounds, including phenolic compounds may play an important role in COVID-19 therapeutics [ 35 , 36 , 37 , 38 ]. However, it is important to emphasize that these findings are tentative, and that the authors only suggest that their antioxidant, anti-platelet and anticoagulant activities may serve as the basis of alternative therapeutic approaches for preventing, or reducing, the risk of CVDs in patients with COVID-19.…”

Section: Introductionmentioning

confidence: 99%

The Antioxidant, Anti-Platelet and Anti-Coagulant Properties of Phenolic Compounds, Associated with Modulation of Hemostasis and Cardiovascular Disease, and Their Possible Effect on COVID-19

Olas

2022

Nutrients

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Patients affected by coronavirus disease 2019 (COVID-19) demonstrate a range of hemostasis dysfunctions, such as coagulation dysfunction and changes in blood platelet function, this being a major cause of death. These complications may also be associated with oxidative stress. Recently, various papers, including some reviews, have suggested that the use of dietary bioactive compounds, including phenolic compounds, may play a significant role in the treatment of COVID-19. However, while some phenolic compounds, such as curcumin, resveratrol, myricetin and scutellarian, have been found to have antiviral effects against COVID-19, recommendations regarding the use of such compounds to prevent or reduce the risk of CVDs during COVID-19 infection remain tentative. The present mini-review examines the antioxidant, anti-platelet and anticoagulant and antiviral activities of selected phenolic compounds and the possible implications for their use in treating CVDs associated with COVID-19. This review also examines whether these phenolic compounds can be promising agents in the modulation of hemostasis and CVDs during COVID-19. While their properties have been well documented in various in vitro and in vivo studies, particularly their positive role in the prophylaxis and treatment of CVDs, less is known regarding their prophylactic potential against CVDs during COVID-19, and no credible evidence exists for their efficiency in humans or animals. In such cases, no in vitro or in vivo studies are available. Therefore, it cannot be unequivocally stated whether treatment with these phenolic compounds offers benefits against CVDs in patients with COVID-19.

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“…Another biochemical and enzyme activity tests showed that the turmeric root extract can significantly constrain the main protease (M pro ) activity of SARS-CoV-2 ( Dound et al, 2021 ). Within the past 3 months, the results of a new in vitro study by Bahun et al (2022) showed the IC 50 of curcumin on the SARS-CoV-2 protease 3CL pro is 11.9 μM, but in another in vitro study by Marín-Palma et al (2021) , results illustrated that curcumin has the EC 50 from 1.14 μg/ml to 6.03 μg/ml in the antiviral effects of several different SARS-CoV-2 variants, whereas the data revealed curcumin has a cytotoxic effects with the CC 50 about 16.5 μg/ml, which is equal to 6.1 μM. The results of the two in vitro studies demonstrate that curcumin has the potential to inhibit the SARS-CoV-2 infection, but its effective and cytotoxicity doses are very close and have some overlapping that needs additional studies to evaluate its practical safe dose and treatment mode of its application for COVID-19 treatment.…”

Section: Introductionmentioning

confidence: 99%

“…M pro as a main protease can catalyze more than 11 proteolytic cleavage sites for nsp generation and without human homologs ( Dai et al, 2020 ); therefore, M pro is considered to be an ideal antiviral target for COVID-19 treatment ( Li and Kang 2020 ). Results of in silico studies show that curcumin/curcuminoids can form strong bonds with the active site of SARS-CoV-2 M pro ( Ibrahim et al, 2020 ; Bahun et al, 2022 ). Due to high binding affinity and its binding with the interface region of M pro may cause the protein conformational changes, indicating that curcumin/curcuminoids could be the potential ligands for COVID-19 therapy ( Ibrahim et al, 2020 ; Li and Kang 2020 ; Kumar M. et al, 2021 ; Mahmud et al, 2021a ; Babaeekhou et al, 2021 ; Teli et al, 2021 ; Halder et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…One more study demonstrated that demethoxycurcumin and bisdemethoxycurcumin had an optimum binding affinity with COVID-19 M pro by molecular modeling and showed the stable state by molecular dynamic (MD) simulation assay, suggesting these could be one of the potential ligands for COVID-19 therapy ( Mulu et al, 2021 ). Unfortunately, there are only two reports with in vitro validation of the inhibitory and selectivity effects of curcumin on SARS-CoV-2 infection to confirm its powerful potential on COVID-19 therapy ( Kandeil et al, 2021 ; Bahun et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth

Fu¹,

Kang³

et al. 2022

Front. Pharmacol.

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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a positive-strand RNA virus, and has rapidly spread worldwide as a pandemic. The vaccines, repurposed drugs, and specific treatments have led to a surge of novel therapies and guidelines nowadays; however, the epidemic of COVID-19 is not yet fully combated and is still in a vital crisis. In repositioning drugs, natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Of note, the predominant curcumoid extracted from turmeric (Curcuma longa L.) including phenolic curcumin influences multiple signaling pathways and has demonstrated to possess anti-inflammatory, antioxidant, antimicrobial, hypoglycemic, wound healing, chemopreventive, chemosensitizing, and radiosensitizing spectrums. In this review, all pieces of current information related to curcumin-used for the treatment and prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through in vitro, in vivo, and in silico studies, clinical trials, and new formulation designs are retrieved to re-evaluate the applications based on the pharmaceutical efficacy of clinical therapy and to provide deep insights into knowledge and strategy about the curcumin’s role as an immune booster, inflammatory modulator, and therapeutic agent against COVID-19. Moreover, this study will also afford a favorable application or approach with evidence based on the drug discovery and development, pharmacology, functional foods, and nutraceuticals for effectively fighting the COVID-19 pandemic.

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Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols

Cited by 87 publications

References 40 publications

Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2

Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2

The Antioxidant, Anti-Platelet and Anti-Coagulant Properties of Phenolic Compounds, Associated with Modulation of Hemostasis and Cardiovascular Disease, and Their Possible Effect on COVID-19

Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth

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