The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Bhupendra Nath Tripathi - One of the best experts on this subject based on the ideXlab platform.
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Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E.
Antiviral research, 2021Co-Authors: Ram Kumar, Nitin Khandelwal, Yogesh Chander, Thachamvally Riyesh, Sanjay Barua, Baldev R Gulati, Yash Pal, Mohammad Afsar, R. K. Dedar, Bhupendra Nath TripathiAbstract: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.
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Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants
Antiviral research, 2017Co-Authors: Nitin Khandelwal, Yogesh Chander, Krishan Dutt Rawat, Thachamvally Riyesh, Chikkahonnaiah Nishanth, Shalini Sharma, Naresh Jindal, Bhupendra Nath Tripathi, Sanjay Barua, Naveen KumarAbstract:At a noncytotoxic concentration, Emetine was found to inhibit replication of DNA viruses [buffalopoxvirus (BPXV) and bovine herpesvirus 1 (BHV-1)] as well as RNA viruses [peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV)]. Using the time-of-addition and virus step-specific assays, we showed that Emetine treatment resulted in reduced synthesis of viral RNA (PPRV and NDV) and DNA (BPXV and BHV-1) as well as inhibiting viral entry (NDV and BHV-1). In addition, Emetine treatment also resulted in decreased synthesis of viral proteins. In a cell free endogenous viral polymerase assay, Emetine was found to significantly inhibit replication of NDV, but not BPXV genome, suggesting that besides directly inhibiting specific viral polymerases, Emetine may also target other factors essentially required for efficient replication of the viral genome. Moreover, Emetine was found to significantly inhibit BPXV-induced pock lesions on chorioallantoic membrane (CAM) along with associated mortality of embryonated chicken eggs. At a lethal dose 50 (LD50) of 126.49 ng/egg and at an effective concentration 50 (EC50) of 3.03 ng/egg, the therapeutic index of the Emetine against BPXV was determined to be 41.74. Emetine was also found to significantly delay NDV-induced mortality in chicken embryos associated with reduced viral titers. Further, Emetine-resistant mutants were not observed upon long-term (P = 25) sequential passage of BPXV and NDV in cell culture. Collectively, we have extended the effective antiviral activity of Emetine against diverse groups of DNA and RNA viruses and propose that Emetine could provide significant therapeutic value against some of these viruses without inducing an antiviral drug-resistant phenotype.
John L. Middlebrook - One of the best experts on this subject based on the ideXlab platform.
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Effects of Emetine on the specific association of T-2 toxin with mammalian cells.
The Journal of pharmacology and experimental therapeutics, 1993Co-Authors: Dennis L. Leatherman, John L. MiddlebrookAbstract:The effects of Emetine on the association of T-2 toxin with Chinese hamster ovary cells were examined. T-2 toxin-cell association at both 4 degrees C and 37 degrees C was reduced by up to 90% after preincubation of cells with Emetine. Emetine-induced reduction in T-2 toxin-cell association was time-, temperature-, and concentration-dependent. A 4-min preincubation with Emetine at physiological temperature was required to develop the maximum inhibitory effect. After brief exposures (< or = 5 min), Emetine's inhibitory effects on toxin-cell association were reversible. However, after longer exposure periods to Emetine (60 min), toxin-cell association was irreversibly blocked. The addition of Emetine to cells prebound with toxin resulted in dissociation at a rate 2 to 3 times slower than a competitive chase with nonlabeled toxin. Emetine did not compete directly for T-2 toxin binding to its receptor on isolated, purified, run-off ribosomes. However, the binding of toxin to purified ribosomes prepared from cells preincubated with Emetine was markedly reduced. Scatchard analysis indicated that Emetine's inhibitory effects on T-2 toxin-cell association were mediated through mixed allosteric and competitive types of inhibition at specific, intracellular, T-2 toxin ribosomal binding sites.
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Effect of Emetine on T-2 toxin-induced inhibition of protein synthesis in mammalian cells.
The Journal of pharmacology and experimental therapeutics, 1993Co-Authors: Dennis L. Leatherman, John L. MiddlebrookAbstract:Chinese hamster ovary cells were used to examine the effect of Emetine upon the toxicity of T-2 toxin and several related trichothecene inhibitors of polypeptide synthesis. Emetine inhibited protein synthesis and T-2 toxin-cell association in a concentration-dependent manner. The dose-response curves for these two effects were nearly identical. Over a narrow concentration range (0.3-3.0 micrograms/ml), Emetine's inhibition of protein synthesis was partially reversible, whereas its inhibition of toxin-cell association was maintained for extended periods. This sustained inhibition of toxin-cell association, resulted in "desensitized" cells with reduced sensitivity to the inhibitory effects of T-2 toxin on protein synthesis. Similar results were obtained when Emetine-preincubated cells were challenged with diacetoxyscirpenol, verrucarin A and roridin A. In contrast, there were no measurable effects of Emetine upon the response of the cells to the less potent trichothecenes, deoxynivalenol, T-2 tetraol and verrucarol. In addition to Emetine, several other inhibitors of polypeptide synthesis were examined for their effects on T-2 toxin-cell association and sensitivity to T-2 toxin. Of these, only cycloheximide inhibited toxin-cell association. Unlike Emetine, sustained protection against the effects of T-2 toxin was not observed with cycloheximide.
Nitin Khandelwal - One of the best experts on this subject based on the ideXlab platform.
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Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E.
Antiviral research, 2021Co-Authors: Ram Kumar, Nitin Khandelwal, Yogesh Chander, Thachamvally Riyesh, Sanjay Barua, Baldev R Gulati, Yash Pal, Mohammad Afsar, R. K. Dedar, Bhupendra Nath TripathiAbstract: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.
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Emetine as an antiviral agent suppresses sars cov 2 replication by inhibiting interaction of viral mrna with eif4e an in vitro study
bioRxiv, 2020Co-Authors: Ram Kumar, Nitin Khandelwal, Yogesh Chander, Thachamvally Riyesh, Sanjay Barua, Baldev R Gulati, Yash Pal, B N Tripathi, Naveen KumarAbstract: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.
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Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants
Antiviral research, 2017Co-Authors: Nitin Khandelwal, Yogesh Chander, Krishan Dutt Rawat, Thachamvally Riyesh, Chikkahonnaiah Nishanth, Shalini Sharma, Naresh Jindal, Bhupendra Nath Tripathi, Sanjay Barua, Naveen KumarAbstract:At a noncytotoxic concentration, Emetine was found to inhibit replication of DNA viruses [buffalopoxvirus (BPXV) and bovine herpesvirus 1 (BHV-1)] as well as RNA viruses [peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV)]. Using the time-of-addition and virus step-specific assays, we showed that Emetine treatment resulted in reduced synthesis of viral RNA (PPRV and NDV) and DNA (BPXV and BHV-1) as well as inhibiting viral entry (NDV and BHV-1). In addition, Emetine treatment also resulted in decreased synthesis of viral proteins. In a cell free endogenous viral polymerase assay, Emetine was found to significantly inhibit replication of NDV, but not BPXV genome, suggesting that besides directly inhibiting specific viral polymerases, Emetine may also target other factors essentially required for efficient replication of the viral genome. Moreover, Emetine was found to significantly inhibit BPXV-induced pock lesions on chorioallantoic membrane (CAM) along with associated mortality of embryonated chicken eggs. At a lethal dose 50 (LD50) of 126.49 ng/egg and at an effective concentration 50 (EC50) of 3.03 ng/egg, the therapeutic index of the Emetine against BPXV was determined to be 41.74. Emetine was also found to significantly delay NDV-induced mortality in chicken embryos associated with reduced viral titers. Further, Emetine-resistant mutants were not observed upon long-term (P = 25) sequential passage of BPXV and NDV in cell culture. Collectively, we have extended the effective antiviral activity of Emetine against diverse groups of DNA and RNA viruses and propose that Emetine could provide significant therapeutic value against some of these viruses without inducing an antiviral drug-resistant phenotype.
Naveen Kumar - One of the best experts on this subject based on the ideXlab platform.
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Emetine as an antiviral agent suppresses sars cov 2 replication by inhibiting interaction of viral mrna with eif4e an in vitro study
bioRxiv, 2020Co-Authors: Ram Kumar, Nitin Khandelwal, Yogesh Chander, Thachamvally Riyesh, Sanjay Barua, Baldev R Gulati, Yash Pal, B N Tripathi, Naveen KumarAbstract: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.
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Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants
Antiviral research, 2017Co-Authors: Nitin Khandelwal, Yogesh Chander, Krishan Dutt Rawat, Thachamvally Riyesh, Chikkahonnaiah Nishanth, Shalini Sharma, Naresh Jindal, Bhupendra Nath Tripathi, Sanjay Barua, Naveen KumarAbstract:At a noncytotoxic concentration, Emetine was found to inhibit replication of DNA viruses [buffalopoxvirus (BPXV) and bovine herpesvirus 1 (BHV-1)] as well as RNA viruses [peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV)]. Using the time-of-addition and virus step-specific assays, we showed that Emetine treatment resulted in reduced synthesis of viral RNA (PPRV and NDV) and DNA (BPXV and BHV-1) as well as inhibiting viral entry (NDV and BHV-1). In addition, Emetine treatment also resulted in decreased synthesis of viral proteins. In a cell free endogenous viral polymerase assay, Emetine was found to significantly inhibit replication of NDV, but not BPXV genome, suggesting that besides directly inhibiting specific viral polymerases, Emetine may also target other factors essentially required for efficient replication of the viral genome. Moreover, Emetine was found to significantly inhibit BPXV-induced pock lesions on chorioallantoic membrane (CAM) along with associated mortality of embryonated chicken eggs. At a lethal dose 50 (LD50) of 126.49 ng/egg and at an effective concentration 50 (EC50) of 3.03 ng/egg, the therapeutic index of the Emetine against BPXV was determined to be 41.74. Emetine was also found to significantly delay NDV-induced mortality in chicken embryos associated with reduced viral titers. Further, Emetine-resistant mutants were not observed upon long-term (P = 25) sequential passage of BPXV and NDV in cell culture. Collectively, we have extended the effective antiviral activity of Emetine against diverse groups of DNA and RNA viruses and propose that Emetine could provide significant therapeutic value against some of these viruses without inducing an antiviral drug-resistant phenotype.
Yogesh Chander - One of the best experts on this subject based on the ideXlab platform.
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Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E.
Antiviral research, 2021Co-Authors: Ram Kumar, Nitin Khandelwal, Yogesh Chander, Thachamvally Riyesh, Sanjay Barua, Baldev R Gulati, Yash Pal, Mohammad Afsar, R. K. Dedar, Bhupendra Nath TripathiAbstract: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.
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Emetine as an antiviral agent suppresses sars cov 2 replication by inhibiting interaction of viral mrna with eif4e an in vitro study
bioRxiv, 2020Co-Authors: Ram Kumar, Nitin Khandelwal, Yogesh Chander, Thachamvally Riyesh, Sanjay Barua, Baldev R Gulati, Yash Pal, B N Tripathi, Naveen KumarAbstract: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.
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Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants
Antiviral research, 2017Co-Authors: Nitin Khandelwal, Yogesh Chander, Krishan Dutt Rawat, Thachamvally Riyesh, Chikkahonnaiah Nishanth, Shalini Sharma, Naresh Jindal, Bhupendra Nath Tripathi, Sanjay Barua, Naveen KumarAbstract:At a noncytotoxic concentration, Emetine was found to inhibit replication of DNA viruses [buffalopoxvirus (BPXV) and bovine herpesvirus 1 (BHV-1)] as well as RNA viruses [peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV)]. Using the time-of-addition and virus step-specific assays, we showed that Emetine treatment resulted in reduced synthesis of viral RNA (PPRV and NDV) and DNA (BPXV and BHV-1) as well as inhibiting viral entry (NDV and BHV-1). In addition, Emetine treatment also resulted in decreased synthesis of viral proteins. In a cell free endogenous viral polymerase assay, Emetine was found to significantly inhibit replication of NDV, but not BPXV genome, suggesting that besides directly inhibiting specific viral polymerases, Emetine may also target other factors essentially required for efficient replication of the viral genome. Moreover, Emetine was found to significantly inhibit BPXV-induced pock lesions on chorioallantoic membrane (CAM) along with associated mortality of embryonated chicken eggs. At a lethal dose 50 (LD50) of 126.49 ng/egg and at an effective concentration 50 (EC50) of 3.03 ng/egg, the therapeutic index of the Emetine against BPXV was determined to be 41.74. Emetine was also found to significantly delay NDV-induced mortality in chicken embryos associated with reduced viral titers. Further, Emetine-resistant mutants were not observed upon long-term (P = 25) sequential passage of BPXV and NDV in cell culture. Collectively, we have extended the effective antiviral activity of Emetine against diverse groups of DNA and RNA viruses and propose that Emetine could provide significant therapeutic value against some of these viruses without inducing an antiviral drug-resistant phenotype.