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Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy

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Abstract

The COVID-19 pandemic that started in 2019 and resulted in significant morbidity and mortality continues to be a significant global health challenge, characterized by inflammation, oxidative stress, and immune system dysfunction.. Developing therapies for preventing or treating COVID-19 remains an important goal for pharmacology and drug development research. Polyphenols are effective against various viral infections and can be extracted and isolated from plants without losing their therapeutic potential. Researchers have developed methods for separating and isolating polyphenols from complex matrices. Polyphenols are effective in treating common viral infections, including COVID-19, and can also boost immunity. Polyphenolic-based antiviral medications can mitigate SARS-CoV-2 enzymes vital to virus replication and infection. Individual polyphenolic triterpenoids, flavonoids, anthraquinonoids, and tannins may also inhibit the SARS-CoV-2 protease. Polyphenol pharmacophore structures identified to date can explain their action and lead to the design of novel anti-COVID-19 compounds. Polyphenol-containing mixtures offer the advantages of a well-recognized safety profile with few known severe side effects. However, studies to date are limited, and further animal studies and randomized controlled trials are needed in future studies. The purpose of this study was to review and present the latest findings on the therapeutic impact of plant-derived polyphenols on COVID-19 infection and its complications. Exploring alternative approaches to traditional therapies could aid in developing novel drugs and remedies against coronavirus infection.

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Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

ACE2:

Angiotensin converting enzyme-2

AMPK:

AMP-activated protein kinase

AMs:

Alveolar macrophages

APCs:

Antigen-presenting cells

ARDS:

Acute respiratory distress syndrome

ATF3:

Activating transcription factor 3

BAL:

Bronchoalveolar lavage

CBG:

Cytosolic β-glucosidase

CCL:

C–C motif chemokine ligand

CD:

Cluster of differentiation

COX:

Cyclooxygenase

CTLs:

Cytotoxic T lymphocytes

DAMPs:

Danger-associated molecular patterns

dsRNA:

Double-stranded RNA

EGCG:

Epigallocatechin gallate

EGFR:

Epidermal growth factor receptor

ERGIC:

Endoplasmic reticulum-Golgi intermediate compartment

ERK:

Extracellular signal-regulated kinase

FOXP3:

Forkhead box P3

HIF-1:

Hypoxia-inducible factor 1

HLA:

Human leukocyte antigen

HRSV:

Human respiratory syncytial virus

IFNγ:

Interferon-γ

Ig:

Immunoglobulin

IκBα:

Inhibitor of κBα

IKKα:

Inhibitory κB kinase α

IL:

Interleukin

ILT:

Immunoglobulin-like transcript

iNOS:

Inducible nitric oxide synthase

JNK/SAPK:

C-jun N-terminal or stress-activated protein kinases

LPH:

Lactase-phlorizin hydrolase

LPSs:

Lipopolysaccharides

MAPK:

Mitogen-activated protein kinase

MBL:

Mannose-bound lectin

MDMs:

Monocyte-derived macrophages

MHC:

Major histocompatibility complex

MIP:

Macrophage inflammatory protein

NADPH:

Nicotinamide adenine dinucleotide phosphate

NETs:

Neutrophil extracellular traps

NF-Κb:

Nuclear factor kappa B

NK:

Natural killer

NLRP-3:

Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3

NO:

Nitric oxide

Nrf-2:

Nuclear factor erythroid 2-related factor 2

NSAIDs:

Non-steroidal anti-inflammatory drugs

PAMPs:

Pathogen-associated molecular patterns

PF:

Pulmonary fibrosis

PIK3CA:

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha

PMNs:

Polymorphonuclear neutrophils

RORγt:

Related orphan receptor gamma t

PPARγ:

Peroxisome proliferator-activated receptor gamma

PRRs:

Pattern recognition receptors

RBD:

Receptor-binding domain

RBM:

Receptor-binding motif

ROS:

Reactive oxygen species

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

SeV:

Sendai virus

STAT:

Signal transducers and activators of transcription

TBX1:

T-box transcription factor

TfR1:

Transferrin receptor protein 1

TLR-4:

Toll like receptor 4

TMPRSS2:

Transmembrane serine protease 2

TNFα:

Tumour necrosis factor α

Th1:

T helper 1

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Author notes

  1. Mahdi Vajdi and Arash Karimi have contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran

    Mahdi Vajdi & Shirin Hassanizadeh

  2. Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

    Arash Karimi

  3. Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahdieh Abbasalizad Farhangi

  4. Department of Community Nutrition, Food Security Research Center, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad Bagherniya & Gholamreza Askari

  5. Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad Bagherniya & Gholamreza Askari

  6. Discipline of Pharmacology, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia

    Basil D. Roufogalis

  7. NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia

    Basil D. Roufogalis

  8. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2P5, Canada

    Neal M. Davies

  9. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  10. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

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All authors have read and approved the manuscript; AS, BDR, MV, and MB conceptualized the review paper. MV, AK, SH, MAF, and MB prepared the original draft. GA, BDR, NMD, and AS were involved in the critical revision of the original draft.

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Vajdi, M., Karimi, A., Hassanizadeh, S. et al. Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy. Pharmacol. Rep 76, 307–327 (2024). https://doi.org/10.1007/s43440-024-00585-6

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