Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E

Kumar, R and Afsar, M and Khandelwal, N and Chander, Y and Riyesh, T and Dedar, RK and Gulati, BR and Pal, Y and Barua, S and Tripathi, BN and Hussain, T and Kumar, N (2021) Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E. In: Antiviral Research, 189 .

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Abstract

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. © 2021 Elsevier B.V.

Item Type:	Journal Article
Publication:	Antiviral Research
Publisher:	Elsevier B.V.
Additional Information:	The copyright for this article belongs to Elsevier B.V.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	29 Mar 2021 11:01
Last Modified:	29 Mar 2021 11:01
URI:	http://eprints.iisc.ac.in/id/eprint/68582

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