1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection
The outbreak of SARS-CoV-2 virus caused more than 80,155,187 confirmed COVID-19 cases worldwide, which has posed a serious threat to global public health and the economy. The development of vaccines and discovery of novel drugs for COVID-19 are urgently needed. Although the FDA-approved SARS-CoV-2 v...
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Frontiers Media S.A.
2021-03-01
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Series: | Frontiers in Pharmacology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.634176/full |
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doaj-330a85dbe2524f17a69964d52fc7b2fa |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rui Hong Chen Li Jun Yang Sami Hamdoun Sami Hamdoun Sookja Kim Chung Sookja Kim Chung Christopher Wai-kei Lam Kai Xi Zhang Xiaoling Guo Chenglai Xia Betty Yuen Kwan Law Vincent Kam Wai Wong |
spellingShingle |
Rui Hong Chen Li Jun Yang Sami Hamdoun Sami Hamdoun Sookja Kim Chung Sookja Kim Chung Christopher Wai-kei Lam Kai Xi Zhang Xiaoling Guo Chenglai Xia Betty Yuen Kwan Law Vincent Kam Wai Wong 1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection Frontiers in Pharmacology 1, 2, 3, 4, 6-pentagalloyl glucose RBD-ACE2 inhibitor SARS-CoV-2 COVID-19 viral infection |
author_facet |
Rui Hong Chen Li Jun Yang Sami Hamdoun Sami Hamdoun Sookja Kim Chung Sookja Kim Chung Christopher Wai-kei Lam Kai Xi Zhang Xiaoling Guo Chenglai Xia Betty Yuen Kwan Law Vincent Kam Wai Wong |
author_sort |
Rui Hong Chen |
title |
1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection |
title_short |
1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection |
title_full |
1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection |
title_fullStr |
1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection |
title_full_unstemmed |
1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection |
title_sort |
1,2,3,4,6-pentagalloyl glucose, a rbd-ace2 binding inhibitor to prevent sars-cov-2 infection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-03-01 |
description |
The outbreak of SARS-CoV-2 virus caused more than 80,155,187 confirmed COVID-19 cases worldwide, which has posed a serious threat to global public health and the economy. The development of vaccines and discovery of novel drugs for COVID-19 are urgently needed. Although the FDA-approved SARS-CoV-2 vaccines has been launched in many countries recently, the strength of safety, stringent storage condition and the possibly short-term immunized efficacy remain as the major challenges in the popularity and recognition of using vaccines against SARS-CoV-2. With the spike-receptor binding domain (RBD) of SARS-CoV-2 being responsible for binding to human angiotensin-converting enzyme 2 receptor (hACE2), ACE2 is identified as the receptor for the entry and viral infection of SARS-CoV-2. In this study, molecular docking and biolayer interferometry (BLI) binding assay were adopted to determine the direct molecular interactions between natural small-molecule, 1,2,3,4,6-Pentagalloyl glucose (PGG) and the spike-RBD of the SARS-CoV-2. Our results showed that PGG preferentially binds to a pocket that contains residues Glu 340 to Lys 356 of spike-RBD with a relatively low binding energy of -8 kcal/mol. BLI assay further confirmed that PGG exhibits a relatively strong binding affinity to SARS-CoV-2-RBD protein in comparison to hACE2. In addition, both ELISA and immunocytochemistry assay proved that PGG blocks SARS-CoV-2-RBD binding to hACE2 dose dependently in cellular level. Notably, PGG was confirmed to abolish the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of wild type SARS-CoV-2 virus in human host cells. Finally, maximal tolerated dose (MTD) studies revealed that up to 200 mg/kg/day of PGG was confirmed orally safe in mice. Our findings suggest that PGG may be a safe and potential antiviral agent against the COVID-19 by blockade the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. Therefore, PGG may be considered as a safe and natural antiviral agent for its possible preventive application in daily anti-virus hygienic products such as a disinfectant spray or face mask. |
topic |
1, 2, 3, 4, 6-pentagalloyl glucose RBD-ACE2 inhibitor SARS-CoV-2 COVID-19 viral infection |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.634176/full |
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doaj-330a85dbe2524f17a69964d52fc7b2fa2021-04-07T08:37:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-03-011210.3389/fphar.2021.6341766341761,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 InfectionRui Hong Chen0Li Jun Yang1Sami Hamdoun2Sami Hamdoun3Sookja Kim Chung4Sookja Kim Chung5Christopher Wai-kei Lam6Kai Xi Zhang7Xiaoling Guo8Chenglai Xia9Betty Yuen Kwan Law10Vincent Kam Wai Wong11Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDepartment of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum, SudanDr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaFaculty of Medicine, Macau University of Science and Technology, Macau, ChinaFaculty of Medicine, Macau University of Science and Technology, Macau, ChinaDr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaFoshan Maternal and Child Health Research Institute, Foshan Women and Children’s Hospital Affiliated to Southern Medical University, Foshan, ChinaFoshan Maternal and Child Health Research Institute, Foshan Women and Children’s Hospital Affiliated to Southern Medical University, Foshan, ChinaDr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaThe outbreak of SARS-CoV-2 virus caused more than 80,155,187 confirmed COVID-19 cases worldwide, which has posed a serious threat to global public health and the economy. The development of vaccines and discovery of novel drugs for COVID-19 are urgently needed. Although the FDA-approved SARS-CoV-2 vaccines has been launched in many countries recently, the strength of safety, stringent storage condition and the possibly short-term immunized efficacy remain as the major challenges in the popularity and recognition of using vaccines against SARS-CoV-2. With the spike-receptor binding domain (RBD) of SARS-CoV-2 being responsible for binding to human angiotensin-converting enzyme 2 receptor (hACE2), ACE2 is identified as the receptor for the entry and viral infection of SARS-CoV-2. In this study, molecular docking and biolayer interferometry (BLI) binding assay were adopted to determine the direct molecular interactions between natural small-molecule, 1,2,3,4,6-Pentagalloyl glucose (PGG) and the spike-RBD of the SARS-CoV-2. Our results showed that PGG preferentially binds to a pocket that contains residues Glu 340 to Lys 356 of spike-RBD with a relatively low binding energy of -8 kcal/mol. BLI assay further confirmed that PGG exhibits a relatively strong binding affinity to SARS-CoV-2-RBD protein in comparison to hACE2. In addition, both ELISA and immunocytochemistry assay proved that PGG blocks SARS-CoV-2-RBD binding to hACE2 dose dependently in cellular level. Notably, PGG was confirmed to abolish the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of wild type SARS-CoV-2 virus in human host cells. Finally, maximal tolerated dose (MTD) studies revealed that up to 200 mg/kg/day of PGG was confirmed orally safe in mice. Our findings suggest that PGG may be a safe and potential antiviral agent against the COVID-19 by blockade the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. Therefore, PGG may be considered as a safe and natural antiviral agent for its possible preventive application in daily anti-virus hygienic products such as a disinfectant spray or face mask.https://www.frontiersin.org/articles/10.3389/fphar.2021.634176/full1, 2, 3, 4, 6-pentagalloyl glucoseRBD-ACE2 inhibitorSARS-CoV-2COVID-19viral infection |