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 Table of Contents  
LETTER TO EDITOR
Year : 2020  |  Volume : 4  |  Issue : 5  |  Page : 108-109

Can Hesperidin be the Key to the Treatment of Severe Acute Respiratory Syndrome COV-2?


1 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Submission14-Jun-2020
Date of Acceptance15-Jul-2020
Date of Web Publication13-Aug-2020

Correspondence Address:
Dr. Atefeh Abedini
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_131_20

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How to cite this article:
Abedini A, Mirtajani SB, Karimzadeh M, Jahangirifard A, Kiani A. Can Hesperidin be the Key to the Treatment of Severe Acute Respiratory Syndrome COV-2?. Biomed Biotechnol Res J 2020;4, Suppl S1:108-9

How to cite this URL:
Abedini A, Mirtajani SB, Karimzadeh M, Jahangirifard A, Kiani A. Can Hesperidin be the Key to the Treatment of Severe Acute Respiratory Syndrome COV-2?. Biomed Biotechnol Res J [serial online] 2020 [cited 2022 Jun 29];4, Suppl S1:108-9. Available from: https://www.bmbtrj.org/text.asp?2020/4/5/108/292080



In the last days of December 2019, there were reports of a coronavirus spreading from Wuhan, China. The infectious nature of the virus, along with its transmission methods, caused it to spread very quickly to other parts of the world. Despite the severity of the infection caused by this virus and its respiratory nature, no specific and complete treatment has yet been provided. This is why severe acute respiratory syndrome (SARS) COV-2 is becoming more and more of a global threat.

The major root of infection with SARS-Cov-2 is through binding of spike protein to the human angiotensin-converting enzyme 2 (hACE2) receptor, which is present in various tissues.[1] Cell-to-cell infection and antibody-dependent enhancement are other roots of infection for SARS-CoV-2 and other viruses. Binding of receptor-binding domain (RBD) to ACE2 is critical for SARS-CoV-2 entrance to the cell and features a crucial role in membrane fusion of the virus.[2] Without proper receptor binding, there is no more S protein conformational change and thus viral entry to cells will decrease.

Flavonoids are one of the important classes of phytochemicals that are well accepted for their beneficial effects on human health.[3] Hesperidin is a type of flavonoids found abundantly in citrus peels. This herbal secondary metabolite is an accepted food additive in some countries. Numerous cases of the therapeutic benefits of hesperidin have been reported so far [Figure 1].
Figure 1: Hesperidin pharmacological effects

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Hesperidin can target the binding between hACE2 and RBD region of spike protein of SARS-CoV-2 by filling the shallow pit of RBD. A hydrogen bond forms between Tyr440 of S protein and the oxygen atom of hesperidin. Hesperidin can hamper the contamination of cells expressing ACE2 receptor by preventing fusion. Therefore, the immune system will have more time to fight the virus. On the other hand, this metabolite reduced lung damage in acute lung injury induced by lipopolysaccharide in animal models of acute respiratory distress syndrome in severe proinflammatory conditions by suppressing the expression of interleukin (IL)-8, tumor necrosis factor-α (TNFα), IL-1 β, IL-12, intercellular adhesion molecule, and vascular cell adhesion molecule 1.[4] Based on available reports, hesperidin increased IL-5, IL-13, macrophage inflammatory protein (MIP)-1α, MIP-1 β, and RANTES in peripheral blood mononuclear cell-derived T-cells expressing Vδ1-T-cell receptor.[5] All of this suggests that hesperidin can be a treatment for viral infections through immune measures. However, in the past, the effect of hesperidin has been observed as an inhibitor for HIV, herpes simplex virus type 2, sindbis virus, and rotavirus.

Anti-cytokine-storm-targeted therapy by the artificial liver blood purification system showed promising results against severe COVID-19 patients.[6] Hence, cytokine modulatory effects of hesperidin may also play a protective role. Therefore, considering the effect of hesperidin on serum levels of cytokines (including IL-4, IL-5, IL-6, IL-8, and IL-13), TNFα, and inflammatory markers can be considered as a possible option to treat patients with SARS-COV-2 infection.

This is important because despite all the studies that have been done on the various properties of hesperidin, no conclusive results of its effects have been reported. However, no comprehensive clinical information on different doses administration of this active ingredient is available yet. Therefore, it is thought that the use of this metabolite could be considered as a potential treatment option for patients with SARS-COV-2.



 
  References Top

1.
Shang J, Wan Y, Liu C, Yount B, Gully K, Yang Y, et al. Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry. PLoS Pathogens 2020;16:E1008392.  Back to cited text no. 1
    
2.
Yan R, Zhang Y, Guo Y, Xia L, Zhou Q. Structural basis for the recognition of the 2019-nCoV by human ACE2. BioRxiv (preprint) 2020.doi: https://doi.org/10.1101/2020.02.19.956946.  Back to cited text no. 2
    
3.
Jucá MM, Cysne Filho FM, de Almeida JC, Mesquita DD, Barriga JR, Dias KC, et al. Flavonoids: Biological activities and therapeutic potential. Nat Prod Res 2020;34:692-705.  Back to cited text no. 3
    
4.
Allam G, Abuelsaad AS. Differential effect of hesperidin on Th1, Th2, Th17, and proinflammatory cytokines production from splenocyte of Schistosoma mansoni-infected mice. Cent Eur J Immunol 2013;38:29-36.  Back to cited text no. 4
    
5.
Yonekawa M, Shimizu M, Kaneko A, Matsumura J, Takahashi H. Suppression of R5-type of HIV-1 in CD4+NKT cells by Vδ1+T cells activated by flavonoid glycosides, hesperidin and linarin. Sci Rep 2019;9:7506.  Back to cited text no. 5
    
6.
Zhang Y, Yu L, Tang L, Zhu M, Jin Y, Wang Z, et al. A promising anti-cytokine-storm targeted therapy for COVID-19: The artificial-liver blood-purification system. Engineering (Beijing) 2020.doi: 10.1016/j.eng.2020.03.006. Epub ahead of print. PMID: 32292628; PMCID: PMC7118608.  Back to cited text no. 6
    


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