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Review
. 2021 Nov 17;22(22):12385.
doi: 10.3390/ijms222212385.

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

Nikola Gligorijevic  1 , Mirjana Radomirovic  2 , Olgica Nedic  1 , Marija Stojadinovic  2 , Urmila Khulal  3   4 , Dragana Stanic-Vucinic  2 , Tanja Cirkovic Velickovic  2   3   4   5
Affiliations
Review

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

Nikola Gligorijevic et al. Int J Mol Sci. .

Abstract

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.

Keywords: SARS-CoV-2; antiviral effects; antiviral targets; polyphenols.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of some phenolic acids and several classes of polyphenols. p-Coumaric acid (A), caffeic acid (B), gallic acid (C), flavan (D), flavone (E), isoflavone (F), chalcone (G), anthocyanidin (H), condensed tannin (I), gallotannin (J), ellagitannin (K), fucol (L), phloroethol (M), fucophloroethol (N), eckol (O), fuhalol (P), and carmalol (Q).
Figure 2
Figure 2
Structure of SARS-CoV-2 virus.
Figure 3
Figure 3
Structure of SARS-CoV-2/ACE 2 receptor complex. The upper, wider part is the S1 domain that interacts with the ACE2 receptor, colored in green, while the lower, narrower part is the S2 domain. Blue squares represent carbohydrates. Image obtained by Cong et al., 2021 [55], PDB entry: 7DF4.
Figure 4
Figure 4
Crystal structure of SARS-CoV-2 3CLpro/Mpro bound to its inhibitor named N3. Inhibitors are located at the two substrate binding sites. Two protomers, A and B, are presented in green and purple. Image obtained by Jin et al., 2020 [57], PDB entry: 6LU7.
Figure 5
Figure 5
Crystal structure of PLpro protease from SARS-CoV-2. Subdomains are color-coded and include N-terminal ubiquitin-like domain in dark blue, thumb subdomain in light blue, palm domain in red and fingers domain in orange. Image obtained by Osipiuk et al., 2021 [60], PDB entry: 7JIW.
Figure 6
Figure 6
Entrance of SARS-CoV-2 virus in a host cell via interaction with ACE2 receptor (I) and its subsequent internal replication (II). Polyphenols are shown to inhibit both modes of action.
Figure 7
Figure 7
Physiological functions affected by COVID-19 and related diseases which the consumption of polyphenols can ameliorate.
See this image and copyright information in PMC

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References

    1. Gupta A., Madhavan M.V., Sehgal K., Nair N., Mahajan S., Sehrawat T.S., Bikdeli B., Ahluwalia N., Ausiello J.C., Wan E.Y., et al. Extrapulmonary manifestations of COVID-19. Nat. Med. 2020;26:1017–1032. doi: 10.1038/s41591-020-0968-3. - DOI - PubMed
    1. Lai C.-C., Ko W.-C., Lee P.-I., Jean S.-S., Hsueh P.-R. Extra-respiratory manifestations of COVID-19. Int. J. Antimicrob. Agents. 2020;56:106024. doi: 10.1016/j.ijantimicag.2020.106024. - DOI - PMC - PubMed
    1. Zheng K.I., Feng G., Liu W., Targher G., Byrne C.D., Zheng M. Extrapulmonary complications of COVID-19: A multisystem disease? J. Med. Virol. 2021;93:323–335. doi: 10.1002/jmv.26294. - DOI - PMC - PubMed
    1. Dong M., Zhang J., Ma X., Tan J., Chen L., Liu S., Xin Y., Zhuang L. ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19. Biomed. Pharmacother. 2020;131:110678. doi: 10.1016/j.biopha.2020.110678. - DOI - PMC - PubMed
    1. Paraiso I.L., Revel J.S., Stevens J.F. Potential use of polyphenols in the battle against COVID-19. Curr. Opin. Food Sci. 2020;32:149–155. doi: 10.1016/j.cofs.2020.08.004. - DOI - PMC - PubMed

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