PMID- 34445310
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20210831
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 16
DP  - 2021 Aug 10
TI  - Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between 
      Spike Protein RBD and Human ACE2 Receptor.
LID - 10.3390/ijms22168604 [doi]
LID - 8604
AB  - 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 (K(D)) for the spike protein (0.63 muM) than 
      hACE2 receptor (1.12 muM), 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.
FAU - Kim, Young Soo
AU  - Kim YS
AUID- ORCID: 0000-0003-0605-1231
AD  - Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 
      Dong-gu, Daegu 41062, Korea.
FAU - Chung, Hwan-Suck
AU  - Chung HS
AUID- ORCID: 0000-0002-5901-0217
AD  - Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 
      Dong-gu, Daegu 41062, Korea.
FAU - Noh, Sang Gyun
AU  - Noh SG
AD  - College of Pharmacy, Pusan National University, Busan 46241, Korea.
FAU - Lee, Bonggi
AU  - Lee B
AD  - Department of Food Science and Nutrition, Pukyong National University, Nam-gu, 
      Daeyeon Dong, Busan 608737, Korea.
FAU - Chung, Hae Young
AU  - Chung HY
AUID- ORCID: 0000-0002-3215-8828
AD  - College of Pharmacy, Pusan National University, Busan 46241, Korea.
FAU - Choi, Jang-Gi
AU  - Choi JG
AD  - Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 
      Dong-gu, Daegu 41062, Korea.
LA  - eng
GR  - KSN2013230/Ministry of Science and ICT, South Korea/
PT  - Journal Article
DEP - 20210810
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Glucosides)
RN  - 0 (Hydrolyzable Tannins)
RN  - 0 (Ligands)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 60976-49-0 (Geraniin)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2/antagonists & inhibitors/chemistry/*metabolism
MH  - Glucosides/chemistry/*pharmacology
MH  - Humans
MH  - Hydrolyzable Tannins/chemistry/*pharmacology
MH  - Ligands
MH  - Molecular Dynamics Simulation
MH  - Protein Interaction Domains and Motifs
MH  - SARS-CoV-2/*drug effects/physiology
MH  - Spike Glycoprotein, Coronavirus/antagonists & inhibitors/chemistry/*metabolism
MH  - Virus Internalization/*drug effects
PMC - PMC8395245
OTO - NOTNLM
OT  - coronavirus disease 2019
OT  - geraniin
OT  - hACE2 receptor
OT  - severe acute respiratory syndrome coronavirus 2
OT  - spike protein
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/28 06:00
MHDA- 2021/09/01 06:00
PMCR- 2021/08/10
CRDT- 2021/08/27 01:23
PHST- 2021/06/07 00:00 [received]
PHST- 2021/07/30 00:00 [revised]
PHST- 2021/07/30 00:00 [accepted]
PHST- 2021/08/27 01:23 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2021/08/10 00:00 [pmc-release]
AID - ijms22168604 [pii]
AID - ijms-22-08604 [pii]
AID - 10.3390/ijms22168604 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Aug 10;22(16):8604. doi: 10.3390/ijms22168604.