Polyphenols Could Prevent SARS-CoV-2 Infection by Modulating the Expression of miRNAs in the Host Cells

Milenković, Dragan; Ruskovska, Tatjana; Rodríguez-Mateos, Ana; Heiß, Christian

doi:10.14336/ad.2021.0223

Cited by 12 publications

(10 citation statements)

References 102 publications

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“…Meanwhile, miR-148a plays another modulator in the proinflammation, a target miRNA of TLR3, which also regulates the IKK/NF-κB pathway, MyD88, and cytokines (IFN-α, IFN-β, IL-6, and IL-8) ( Guo et al, 2020 ). Some studies predict that miR-148a is a high potential candidate for targeting the SARS-CoV-2 genome through bioinformatics ( Saçar Demirci and Adan, 2020 ; Milenkovic et al, 2021 ). Although the regulation among miR-148b-5p, let-7a-5p , and cytokine production was not elaborate, Virofree stimulated these two miRNAs’ expression levels ( Figure 2A ; Supplementary Figure S4 ) and reduced TNF-α ( Figure 2C ).…”

Section: Discussionmentioning

confidence: 99%

Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2

et al. 2022

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Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading.

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Section: Discussionmentioning

confidence: 99%

Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2

et al. 2022

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“…Natural polyphenols are powerful antioxidants and protect against chronic diseases by altering cell signaling pathways and regulating the expression of antioxidant-related genes, indicating that dietary polyphenolic compounds have potential benefits for the prevention of SARS-CoV-2 infection. A limited number of studies have revealed that dietary polyphenolic compounds may act directly against coronaviruses in vitro by modulating expression of host miRNAs 105 , 106 . In a recent review, authors identified 125 polyphenols-modulating host miRNAs and 644 miRNAs that can interact with SARS-CoV-2 genome by performing literature search 106 .…”

Section: Prognostic Biomarkersmentioning

confidence: 99%

“…A limited number of studies have revealed that dietary polyphenolic compounds may act directly against coronaviruses in vitro by modulating expression of host miRNAs 105 , 106 . In a recent review, authors identified 125 polyphenols-modulating host miRNAs and 644 miRNAs that can interact with SARS-CoV-2 genome by performing literature search 106 . Comparison of two groups of miRNA candidates revealed 17 host miRNAs with both capacity to interact with SARS-CoV-2 genome and which expression can be regulate by polyphenols, including hsa-let-7a-3p, has-miR-25-5p, hsa-miR-1246, hsa-miR-125a-5p, hsa-miR-1262, hsa-miR-1290, hsa-miR-148a-5p, hsa-miR-154-3p, hsa-miR-21-3p, hsa-miR-320c, hsa-miR-335-5p, has-miR-34a-5p, hsa-miR-377-5p, hsa-miR-455-3p, has-miR-499a-5p, hsa-miR-544a and hsa-miR-744-3p 106 .…”

Section: Prognostic Biomarkersmentioning

confidence: 99%

“…In a recent review, authors identified 125 polyphenols-modulating host miRNAs and 644 miRNAs that can interact with SARS-CoV-2 genome by performing literature search 106 . Comparison of two groups of miRNA candidates revealed 17 host miRNAs with both capacity to interact with SARS-CoV-2 genome and which expression can be regulate by polyphenols, including hsa-let-7a-3p, has-miR-25-5p, hsa-miR-1246, hsa-miR-125a-5p, hsa-miR-1262, hsa-miR-1290, hsa-miR-148a-5p, hsa-miR-154-3p, hsa-miR-21-3p, hsa-miR-320c, hsa-miR-335-5p, has-miR-34a-5p, hsa-miR-377-5p, hsa-miR-455-3p, has-miR-499a-5p, hsa-miR-544a and hsa-miR-744-3p 106 . These polyphenols-induced miRNAs suggested that exerted anti-SARS-CoV-2 capacity by influencing processes of viral replication or entry.…”

Section: Prognostic Biomarkersmentioning

confidence: 99%

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The emerging role of miRNAs in the pathogenesis of COVID-19: Protective effects of nutraceutical polyphenolic compounds against SARS-CoV-2 infection

Yang¹,

Chen²,

Liu³

et al. 2022

Int. J. Med. Sci.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause immunosuppression and cytokine storm, leading to lung damage and death. The clinical efficacy of anti-SARS-CoV-2 drugs in preventing viral entry into host cells and suppressing viral replication remains inadequate. MicroRNAs (miRNAs) are crucial to the immune response to and pathogenesis of coronaviruses, such as SARS-CoV-2. However, the specific roles of miRNAs in the life cycle of SARS-CoV-2 remain unclear. miRNAs can participate in SARS-CoV-2 infection and pathogenesis through at least four possible mechanisms: 1. host cell miRNA expression interfering with SARS-CoV-2 cell entry, 2. SARS-CoV-2-derived RNA transcripts acting as competitive endogenous RNAs (ceRNAs) that may attenuate host cell miRNA expression, 3. host cell miRNA expression modulating SARS-CoV-2 replication, and 4. SARS-CoV-2-encoded miRNAs silencing the expression of host protein-coding genes. SARS-CoV-2-related miRNAs may be used as diagnostic or prognostic biomarkers for predicting outcomes among patients with SARS-CoV-2 infection. Furthermore, accumulating evidence suggests that dietary polyphenolic compounds may protect against SARS-CoV-2 infection by modulating host cell miRNA expression. These findings have major implications for the future diagnosis and treatment of COVID-19.

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“…Similarly, the role of key medicinal/nutritional antioxidants, including polyphenols, in the antiviral immune response in COVID-19 [26], mechanism of polyphenol action in COVID-19 in comparison to other acute infectious diseases [27], potential of polyphenols in reducing COVID-19 cytokine storm [28,29], and potential of polyphenols in tuning of autophagy and ubiquitin-proteasome system pathways in COVID-19 [30] were reviewed. The use of tea polyphenols in prophylaxis and treatment of COVID-19 [31,32]; polyphenol potential for modulating the expression of host microRNAs that play role in SARS-CoV-2 infection [33]; and beneficial effects of polyphenols against the COVID-19-induced lung damage and associated systemic effects based on predictive, preventive, and personalized medicine (3PM) were also critically studied [34].…”

Section: Health Effects Of Polyphenols Related To Covid-19mentioning

confidence: 99%

Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention

Gligorijević

Radomirović

Nedić

et al. 2021

IJMS

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The worldwide outbreak of COVID-19 was caused by a pathogenic virus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Therapies against SARS-CoV-2 target the virus or human cells or the immune system. However, therapies based on specific antibodies, such as vaccines and monoclonal antibodies, may become inefficient enough when the virus changes its antigenicity due to mutations. Polyphenols are the major class of bioactive compounds in nature, exerting diverse health effects based on their direct antioxidant activity and their effects in the modulation of intracellular signaling. There are currently numerous clinical trials investigating the effects of polyphenols in prophylaxis and the treatment of COVID-19, from symptomatic, via moderate and severe COVID-19 treatment, to anti-fibrotic treatment in discharged COVID-19 patients. Antiviral activities of polyphenols and their impact on immune system modulation could serve as a solid basis for developing polyphenol-based natural approaches for preventing and treating COVID-19.

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Polyphenols Could Prevent SARS-CoV-2 Infection by Modulating the Expression of miRNAs in the Host Cells

Cited by 12 publications

References 102 publications

Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2

Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2

The emerging role of miRNAs in the pathogenesis of COVID-19: Protective effects of nutraceutical polyphenolic compounds against SARS-CoV-2 infection

Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention

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