Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E.
Animals
Antiviral Agents
/ pharmacology
Chick Embryo
Chlorocebus aethiops
Coronavirus Infections
/ drug therapy
Emetine
/ pharmacology
Eukaryotic Initiation Factor-4E
/ metabolism
Infectious bronchitis virus
/ drug effects
Protein Binding
/ drug effects
RNA, Messenger
/ metabolism
RNA, Viral
/ metabolism
SARS-CoV-2
/ drug effects
Signal Transduction
Vero Cells
Antiviral efficacy
Emetine
IBV
In silico binding
SARS-CoV-2
eIF4E
Journal
Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
28
11
2020
revised:
23
02
2021
accepted:
27
02
2021
pubmed:
13
3
2021
medline:
29
4
2021
entrez:
12
3
2021
Statut:
ppublish
Résumé
Emetine is a FDA-approved drug for the treatment of amebiasis. Previously we demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. In this study, we evaluated the in vitro antiviral efficacy of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and found it to be a low nanomolar (nM) inhibitor. Interestingly, emetine exhibited protective efficacy against lethal challenge with infectious bronchitis virus (IBV; a chicken coronavirus) in the embryonated chicken egg infection model. Emetine treatment led to a decrease in viral RNA and protein synthesis without affecting other steps of viral life cycle such as attachment, entry and budding. In a chromatin immunoprecipitation (CHIP) assay, emetine was shown to disrupt the binding of SARS-CoV-2 mRNA with eIF4E (eukaryotic translation initiation factor 4E, a cellular cap-binding protein required for initiation of protein translation). Further, molecular docking and molecular dynamics simulation studies suggested that emetine may bind to the cap-binding pocket of eIF4E, in a similar conformation as m7-GTP binds. Additionally, SARS-CoV-2 was shown to exploit ERK/MNK1/eIF4E signalling pathway for its effective replication in the target cells. Collectively our results suggest that further detailed evaluation of emetine as a potential treatment for COVID-19 may be warranted.
Identifiants
pubmed: 33711336
pii: S0166-3542(21)00046-2
doi: 10.1016/j.antiviral.2021.105056
pmc: PMC7943376
pii:
doi:
Substances chimiques
Antiviral Agents
0
Eukaryotic Initiation Factor-4E
0
RNA, Messenger
0
RNA, Viral
0
Emetine
X8D5EPO80M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105056Subventions
Organisme : DBT-Wellcome Trust India Alliance
ID : IA/I/17/2/503313
Pays : India
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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