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Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs

RNA interference, mediated by short interfering RNAs (siRNAs), has been shown to have activity against a wide range of viruses and is a promising new antiviral therapy. Using multiple siRNAs that target conserved areas of the genome allows for increased chances of antiviral activity against differen...

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Autor principal: O’Brien, Lyn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier B.V. 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114223/
https://www.ncbi.nlm.nih.gov/pubmed/17157930
http://dx.doi.org/10.1016/j.antiviral.2006.11.007
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author O’Brien, Lyn
author_facet O’Brien, Lyn
author_sort O’Brien, Lyn
collection PubMed
description RNA interference, mediated by short interfering RNAs (siRNAs), has been shown to have activity against a wide range of viruses and is a promising new antiviral therapy. Using multiple siRNAs that target conserved areas of the genome allows for increased chances of antiviral activity against different viral strains and also helps to prevent the emergence of escape mutants. In this study, four siRNAs were designed to target areas of conserved sequence between divergent strains of Venezuelan equine encephalitis virus (VEEV). A pool of these siRNAs inhibited the replication of all six strains of VEEV tested. A single nucleotide mismatch at the extreme 3′ end of one of the siRNA sense strands did not affect antiviral activity but other mutations were not tolerated. Two strains of VEEV were tested for their abilities to overcome the inhibitory effects of RNA interference following 10 consecutive incubations in the presence of siRNAs. One strain remained susceptible throughout the course of the experiment but the other strain became resistant to the activity of siRNAs. Sequence analysis of the siRNA target sites in this strain showed that no mutations had been generated, indicating that the virus may had become resistant in some other manner. In the absence of effective antiviral drugs and vaccines to combat VEEV infection, these siRNAs offer a potential new therapeutic approach but, as with all antimicrobial agents, caution needs to be exercised with respect to the generation of resistance.
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spelling pubmed-71142232020-04-02 Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs O’Brien, Lyn Antiviral Res Article RNA interference, mediated by short interfering RNAs (siRNAs), has been shown to have activity against a wide range of viruses and is a promising new antiviral therapy. Using multiple siRNAs that target conserved areas of the genome allows for increased chances of antiviral activity against different viral strains and also helps to prevent the emergence of escape mutants. In this study, four siRNAs were designed to target areas of conserved sequence between divergent strains of Venezuelan equine encephalitis virus (VEEV). A pool of these siRNAs inhibited the replication of all six strains of VEEV tested. A single nucleotide mismatch at the extreme 3′ end of one of the siRNA sense strands did not affect antiviral activity but other mutations were not tolerated. Two strains of VEEV were tested for their abilities to overcome the inhibitory effects of RNA interference following 10 consecutive incubations in the presence of siRNAs. One strain remained susceptible throughout the course of the experiment but the other strain became resistant to the activity of siRNAs. Sequence analysis of the siRNA target sites in this strain showed that no mutations had been generated, indicating that the virus may had become resistant in some other manner. In the absence of effective antiviral drugs and vaccines to combat VEEV infection, these siRNAs offer a potential new therapeutic approach but, as with all antimicrobial agents, caution needs to be exercised with respect to the generation of resistance. Published by Elsevier B.V. 2007-07 2006-12-04 /pmc/articles/PMC7114223/ /pubmed/17157930 http://dx.doi.org/10.1016/j.antiviral.2006.11.007 Text en Crown copyright © 2006 Published by Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
O’Brien, Lyn
Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs
title Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs
title_full Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs
title_fullStr Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs
title_full_unstemmed Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs
title_short Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs
title_sort inhibition of multiple strains of venezuelan equine encephalitis virus by a pool of four short interfering rnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114223/
https://www.ncbi.nlm.nih.gov/pubmed/17157930
http://dx.doi.org/10.1016/j.antiviral.2006.11.007
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