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1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection.
Chen, Rui Hong; Yang, Li Jun; Hamdoun, Sami; Chung, Sookja Kim; Lam, Christopher Wai-Kei; Zhang, Kai Xi; Guo, Xiaoling; Xia, Chenglai; Law, Betty Yuen Kwan; Wong, Vincent Kam Wai.
  • Chen RH; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
  • Yang LJ; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
  • Hamdoun S; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
  • Chung SK; Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan.
  • Lam CW; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
  • Zhang KX; Faculty of Medicine, Macau University of Science and Technology, Macau, China.
  • Guo X; Faculty of Medicine, Macau University of Science and Technology, Macau, China.
  • Xia C; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
  • Law BYK; Foshan Maternal and Child Health Research Institute, Foshan Women and Children's Hospital Affiliated to Southern Medical University, Foshan, China.
  • Wong VKW; Foshan Maternal and Child Health Research Institute, Foshan Women and Children's Hospital Affiliated to Southern Medical University, Foshan, China.
Front Pharmacol ; 12: 634176, 2021.
Article in English | MEDLINE | ID: covidwho-1150704
Semantic information from SemMedBD (by NLM)
1. Inhibitor PREVENTS COVID-19
Subject
Inhibitor
Predicate
PREVENTS
Object
COVID-19
2. Pharmaceutical Preparations TREATS COVID-19
Subject
Pharmaceutical Preparations
Predicate
TREATS
Object
COVID-19
3. Challenge USES Vaccines
Subject
Challenge
Predicate
USES
Object
Vaccines
4. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
5. ACE2 gene|ACE2 INTERACTS_WITH angiotensin converting enzyme 2
Subject
ACE2 gene|ACE2
Predicate
INTERACTS_WITH
Object
angiotensin converting enzyme 2
6. Study MEASURES Binding (Molecular Function)
Subject
Study
Predicate
MEASURES
Object
Binding (Molecular Function)
7. Assay USES Immunocytochemistry
Subject
Assay
Predicate
USES
Object
Immunocytochemistry
8. Cells LOCATION_OF angiotensin converting enzyme 2
Subject
Cells
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
9. pentagalloylglucose DISRUPTS Communicable Diseases
Subject
pentagalloylglucose
Predicate
DISRUPTS
Object
Communicable Diseases
10. pentagalloylglucose TREATS Mus
Subject
pentagalloylglucose
Predicate
TREATS
Object
Mus
11. Inhibitor PREVENTS COVID-19
Subject
Inhibitor
Predicate
PREVENTS
Object
COVID-19
12. Pharmaceutical Preparations TREATS COVID-19
Subject
Pharmaceutical Preparations
Predicate
TREATS
Object
COVID-19
13. Challenge USES Vaccines
Subject
Challenge
Predicate
USES
Object
Vaccines
14. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
15. ACE2 gene|ACE2 INTERACTS_WITH angiotensin converting enzyme 2
Subject
ACE2 gene|ACE2
Predicate
INTERACTS_WITH
Object
angiotensin converting enzyme 2
16. Study MEASURES Binding (Molecular Function)
Subject
Study
Predicate
MEASURES
Object
Binding (Molecular Function)
17. Assay USES Immunocytochemistry
Subject
Assay
Predicate
USES
Object
Immunocytochemistry
18. Cells LOCATION_OF angiotensin converting enzyme 2
Subject
Cells
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
19. pentagalloylglucose DISRUPTS Communicable Diseases
Subject
pentagalloylglucose
Predicate
DISRUPTS
Object
Communicable Diseases
20. pentagalloylglucose TREATS Mus
Subject
pentagalloylglucose
Predicate
TREATS
Object
Mus
ABSTRACT
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.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Prognostic study Topics: Vaccines Language: English Journal: Front Pharmacol Year: 2021 Document Type: Article Affiliation country: Fphar.2021.634176

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Prognostic study Topics: Vaccines Language: English Journal: Front Pharmacol Year: 2021 Document Type: Article Affiliation country: Fphar.2021.634176