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Volume 20, Issue 10
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Background

In the search for anti-COVID-19 therapy, 1,2,3,4,6-pentakis-O-galloyl-β-D-glucopyranoside, a natural polyphenolic compound isolated from many traditional medicinal herbs, has been reported as an RBD-ACE2 binding inhibitor and as a broad-spectrum anti-coronaviral inhibitor targeting the main protease and RNA-dependent RNA polymerase of SARS-CoV-2. To facilitate the structure-activity relationship studies of 1,2,3,4,6-pentakis-O-galloyl-β-D-glucopyranoside, we describe its chemical synthesis and characterization, as well as its activity towards the SARS-CoV-2 spike interaction with host ACE2 receptor.

Methods

1,2,3,4,6-Pentakis-O-galloyl-β-D-glucopyranoside was synthesized in two quantitative steps from 3,4,5-tribenzyloxybenzoic acid and β-D-glucopyranoside: DCC-mediated esterification and palladium-catalyzed per-debenzylation. The synthesized molecule was evaluated using a SARS-CoV-2 spike trimer (S1 + S2) ACE2 inhibitor screening colorimetric assay kit, SARS-CoV-2 spike S1 RBD ACE2 inhibitor screening assay kit, and a cellular neutralization assay using the Spike (SARS-CoV-2) Pseudotyped Lentivirus, ACE2-HEK293 recombinant cell line.

Results

The chemically synthesized product blocked the binding of the spike trimer of SARS-CoV-2 to the human ACE2 receptor with IC=22±2 µM. It also blocked ACE2: spike RBD binding with IC=27±3 µM. Importantly, it inhibited the infectivity of SARS2-CoV2-Spike pseudotyped lentivirus on the ACE2 HEK293 cell line with IC=20±2 µM.

Conclusion

Overall, the chemically synthesized 1,2,3,4,6-pentakis-O-galloyl-β-D-glucopyranoside represents a lead molecule to develop anti-SARS-CoV-2 therapies that block the initial stage of the viral infection by blocking the virus entry to the host cell.

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2024-12-01
2025-02-17

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/content/journals/mc/10.2174/0115734064302693240711114948
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Chemically Synthesized 1,2,3,4,6-Pentakis-O-Galloyl-β-D-Glucopyranoside Blocks SARS-CoV-2 Spike Interaction with Host ACE-2 Receptor
Med. Chem. 20, 986 (2024); https://doi.org/10.2174/0115734064302693240711114948
/content/journals/mc/10.2174/0115734064302693240711114948
/content/journals/mc/10.2174/0115734064302693240711114948
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  • Article Type:     Rapid Communication
Keyword(s): ACE2; HEK293; Pentagalloylglucose; SARS-CoV-2; spike protein; viral entry

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