Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection

Fang-Ju Cheng; Thanh-Kieu Huynh; Chia-Shin Yang; Dai-Wei Hu; Yi-Cheng Shen; Chih-Yen Tu; Yang-Chang Wu; Chih-Hsin Tang; Wei-Chien Huang; Yeh Chen; Chien-Yi Ho

doi:10.3390/nu13082800

Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection

Nutrients. 2021 Aug 16;13(8):2800. doi: 10.3390/nu13082800.

Authors

Fang-Ju Cheng¹, Thanh-Kieu Huynh², Chia-Shin Yang³, Dai-Wei Hu², Yi-Cheng Shen^{2

4}, Chih-Yen Tu^{4

5}, Yang-Chang Wu^{6

7

8}, Chih-Hsin Tang^{2

5}, Wei-Chien Huang^{1

2

8

9}, Yeh Chen^{1

3}, Chien-Yi Ho^{10

11}

Affiliations

¹ Drug Development Center, China Medical University, Taichung 404, Taiwan.
² Graduate Institute of Biomedical Science, China Medical University, Taichung 404, Taiwan.
³ Institute of New Drug Development, China Medical University, Taichung 404, Taiwan.
⁴ Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, China Medical University Hospital, Taichung 404, Taiwan.
⁵ School of Medicine, China Medical University, Taichung 404, Taiwan.
⁶ Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan.
⁷ Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
⁸ Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung 404, Taiwan.
⁹ Research Center for Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan.
¹⁰ Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404, Taiwan.
¹¹ Division of Family Medicine, Physical Examination Center, Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan.

Abstract

Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.

Keywords: 501Y.v2; ACE2; D614G; SARS-CoV-2; TMPRSS2; hesperidin.

MeSH terms

Angiotensin-Converting Enzyme 2 / chemistry
Angiotensin-Converting Enzyme 2 / metabolism
Animals
COVID-19 / metabolism
COVID-19 / virology
COVID-19 Drug Treatment*
Cell Line, Tumor
Chlorocebus aethiops
Coronavirus Papain-Like Proteases / chemistry
Coronavirus Papain-Like Proteases / metabolism
Hesperidin / chemistry*
Hesperidin / pharmacology*
Humans
Molecular Docking Simulation
SARS-CoV-2 / drug effects*
SARS-CoV-2 / metabolism
Serine Endopeptidases / chemistry
Serine Endopeptidases / drug effects
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / metabolism
Vero Cells

Substances

Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Hesperidin
ACE2 protein, human
Angiotensin-Converting Enzyme 2
Serine Endopeptidases
TMPRSS2 protein, human
Coronavirus Papain-Like Proteases
papain-like protease, SARS-CoV-2
hesperetin

Abstract

MeSH terms

Substances

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