Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between Spike Protein RBD and Human ACE2 Receptor.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the development of vaccines, the emergence of SARS-CoV-2 variants and the absence of effective therapeutics demand the continual investigation of COVID-19. Natural products containing active ingredients may be good therapeutic candidates. Here, we investigated the effectiveness of geraniin, the main ingredient in medical plants Elaeocarpus sylvestris var. ellipticus and Nephelium lappaceum, for treating COVID-19. The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (hACE2) receptor to initiate virus entry into cells; viral entry may be an important target of COVID-19 therapeutics. Geraniin was found to effectively block the binding between the SARS-CoV-2 spike protein and hACE2 receptor in competitive enzyme-linked immunosorbent assay, suggesting that geraniin might inhibit the entry of SARS-CoV-2 into human epithelial cells. Geraniin also demonstrated a high affinity to both proteins despite a relatively lower equilibrium dissociation constant (KD) for the spike protein (0.63 μM) than hACE2 receptor (1.12 μM), according to biolayer interferometry-based analysis. In silico analysis indicated geraniin's interaction with the residues functionally important in the binding between the two proteins. Thus, geraniin is a promising therapeutic agent for COVID-19 by blocking SARS-CoV-2's entry into human cells.

• Authors: Young Soo Kim, Hwan-Suck Chung, Sang Gyun Noh, Bonggi Lee, Hae Young Chung, Jang-Gi Choi
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 16 (Aug 10 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34445310 (Publication Type: Journal Article)

Chemical References

• Glucosides
• Hydrolyzable Tannins
• Ligands
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2
• Geraniin
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2 (antagonists & inhibitors, chemistry, metabolism)
• Glucosides (chemistry, pharmacology)
• Humans
• Hydrolyzable Tannins (chemistry, pharmacology)
• Ligands
• Molecular Dynamics Simulation
• Protein Interaction Domains and Motifs
• SARS-CoV-2 (drug effects, physiology)
• Spike Glycoprotein, Coronavirus (antagonists & inhibitors, chemistry, metabolism)
• Virus Internalization (drug effects)