Peimine inhibits variants of SARS-CoV-2 cell entry via blocking the interaction between viral spike protein and ACE2.
Angiotensin-Converting Enzyme 2
/ genetics
Binding Sites
COVID-19 Vaccines
Cevanes
Glycoproteins
Humans
Molecular Docking Simulation
Peptidyl-Dipeptidase A
/ chemistry
Protein Binding
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ chemistry
Viral Proteins
/ metabolism
Virus Internalization
COVID-19 Drug Treatment
variants of concern
ACE2
Fritillaria
SARS-CoV-2
peimine
Journal
Journal of food biochemistry
ISSN: 1745-4514
Titre abrégé: J Food Biochem
Pays: United States
ID NLM: 7706045
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
04
07
2022
received:
30
05
2022
accepted:
13
07
2022
pubmed:
28
7
2022
medline:
13
10
2022
entrez:
27
7
2022
Statut:
ppublish
Résumé
Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several vaccines against SARS-CoV-2 have been approved; however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID-19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS-CoV-2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS-CoV-2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu-3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS-CoV-2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID-19 patients.
Identifiants
pubmed: 35894128
doi: 10.1111/jfbc.14354
pmc: PMC9353385
doi:
Substances chimiques
COVID-19 Vaccines
0
Cevanes
0
Glycoproteins
0
Spike Glycoprotein, Coronavirus
0
Viral Proteins
0
spike protein, SARS-CoV-2
0
verticine
34QDF8UFSY
Peptidyl-Dipeptidase A
EC 3.4.15.1
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14354Subventions
Organisme : China Medical University
Organisme : China Medical University Hospital
Organisme : Ministry of Science and Technology, Taiwan
Informations de copyright
© 2022 Wiley Periodicals LLC.
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