Emetine as an antiviral agent suppresses SARS-CoV-2 replication by inhibitinginteraction of viral mRNAwith eIF4E: Anin vitrostudy

Abstract

Emetine is a FDA-approved drug for the treatment of amebiasis. In the recent times we had also demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. Following emergence of the COVID-19, we further evaluated thein vitro antiviral activity of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The therapeutic index of emetine was determined to be 10910.4, at a cytotoxic concentration 50 (CC50) of 1603.8 nM and effective concentration 50 (EC50) of 0.147 nM.Besides, we also demonstrated the protective efficacy of emetine against lethal challenge with infectious bronchitis virus (IBV; a chicken coronavirus) in the embryonated chicken egg infection model. Emetine treatment was shown to decrease 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 RNA with eIF4E (eukaryotic translation initiation factor 4E, a cellular cap-binding protein required for initiation ofprotein translation). Further, SARS-CoV-2 was shown to exploit ERK/MNK1/eIF4E signalling pathwayfor its effective replication in the target cells. To conclude, emetine targets SARS-CoV-2 protein synthesis which is mediated via inhibiting the interaction of SARS-CoV-2 RNA with eIF4E. This is a novel mechanistic insight on the antiviral efficacy of emetine. In vitro antiviral efficacy against SARS-CoV-2 and its ability to protect chicken embryos against IBV suggests that emetine could be repurposed to treat COVID-19.

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms

“…eir report was in line with that of Choy et al in showing in vitro anti-SARS-CoV-2 activities of emetine and homoharringtonine, at 2.55 and 0.46 μM, respectively [11,55]. Additionally, Kumar et al showed that emetine (2.3 ng/egg) inhibited SARS-CoV-2 replication via suppressing viral proteins such as viral polymerase in the infecting chicken embryonic model with IBV (chicken coronavirus) [56]. Also, another study showed that homoharringtonine strongly interacted with SARS-CoV-2 S protein among eleven anti-SARS-CoV alkaloids with a LibDock score of 109.11 kcal/mol [57].…”

Repurposed Therapeutic Strategies towards COVID-19 Potential Targets Based on Genomics and Protein Structure Remodeling

“…Were found to inhibit SARS-CoV helicase (nsp13) via inhibition of ATPase activity being a potential phytochemical inhibitor [73,74]. Emetine could be re-purposed to treat COVID-19 based on the in-vitro antiviral activity against SARS-CoV-2 and its ability to shield chicken embryos from IBV [75].…”

SARS-CoV-2 spike protein and RNA dependent RNA polymerase as targets for drug and vaccine development: A review

“…Treatment with Emetine could decrease the replication of virus by decreasing the synthesis of RNA and protein. Emetine could disrupt the binding of the eukaryotic translation initiation factor (a cap-binding protein needed for translation) with SARS-CoV-2 RNA in an investigation using chromatin immunoprecipitation assay [73] , [76] .…”