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Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants.

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Title Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants.
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Creator Khandelwal N, Chander Y, Rawat KD, Riyesh T, Nishanth C, Sharma S, Jindal N, Tripathi BN, Barua S, Kumar N
 
Subject Emetine ,Antiviral efficacy, Antiviral drug resistance, RNA synthesis, DNA synthesis
 
Description Not Available
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.
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Date 2019-12-02T05:31:59Z
2019-12-02T05:31:59Z
2017-06-15
 
Type Journal
 
Identifier Not Available
Not Available
http://krishi.icar.gov.in/jspui/handle/123456789/26181
 
Language English
 
Relation Not Available;
 
Publisher Not Available