To accelerate the Zika beat: Candidate design for RNA interference-based therapy.
Identifieur interne : 000C14 ( Main/Exploration ); précédent : 000C13; suivant : 000C15To accelerate the Zika beat: Candidate design for RNA interference-based therapy.
Auteurs : M. Giulietti [Italie] ; A. Righetti [Italie] ; L. Cianfruglia [Italie] ; B. Šabanovi [Italie] ; T. Armeni [Italie] ; G. Principato [Italie] ; F. Piva [Italie]Source :
- Virus research [ 1872-7492 ] ; 2018.
Descripteurs français
- KwdFr :
- Antiviraux (pharmacologie), Antiviraux (usage thérapeutique), Biologie informatique, Génome viral, Humains, Infection par le virus Zika (), Petit ARN interférent (génétique), Petit ARN interférent (pharmacologie), Petit ARN interférent (usage thérapeutique), Réplication virale (), Sécurité, Thérapie moléculaire ciblée, Thérapie par l'interférence par ARN, Virus Zika (), Virus Zika (génétique), Virus Zika (physiologie).
- MESH :
- génétique : Petit ARN interférent, Virus Zika.
- pharmacologie : Antiviraux, Petit ARN interférent.
- physiologie : Virus Zika.
- usage thérapeutique : Antiviraux, Petit ARN interférent.
- Biologie informatique, Génome viral, Humains, Infection par le virus Zika, Réplication virale, Sécurité, Thérapie moléculaire ciblée, Thérapie par l'interférence par ARN, Virus Zika.
English descriptors
- KwdEn :
- Antiviral Agents (pharmacology), Antiviral Agents (therapeutic use), Computational Biology, Genome, Viral, Humans, Molecular Targeted Therapy, RNA, Small Interfering (genetics), RNA, Small Interfering (pharmacology), RNA, Small Interfering (therapeutic use), RNAi Therapeutics, Safety, Virus Replication (drug effects), Zika Virus (drug effects), Zika Virus (genetics), Zika Virus (physiology), Zika Virus Infection (therapy).
- MESH :
- chemical , genetics : RNA, Small Interfering.
- chemical , pharmacology : Antiviral Agents, RNA, Small Interfering.
- chemical , therapeutic use : Antiviral Agents, RNA, Small Interfering.
- drug effects : Virus Replication, Zika Virus.
- genetics : Zika Virus.
- physiology : Zika Virus.
- therapy : Zika Virus Infection.
- Computational Biology, Genome, Viral, Humans, Molecular Targeted Therapy, RNAi Therapeutics, Safety.
Abstract
Zika virus infection is associated with the development of severe neurological disorders in adults and newborns. Although at the moment Zika virus outbreak is not threatening to become again an emergency, infection cases are still being sporadically reported and there is still no effective therapy available. A possible treatment to suppress Zika replication is represented by short interfering RNAs (siRNAs), since they have been successfully used even against Ebola, H5N1 and SARS viruses and clinical trials of siRNA-based drugs are ongoing. In order to speed up the time consuming experimental validation of effective siRNAs, we have performed a comprehensive bioinformatic analysis to design only a few promising siRNAs against Zika virus. Besides siRNA efficacy, we paid attention to broad-spectrum antiviral activity, obtained by analysing all known Zika genomes, and siRNA safety, by excluding siRNAs that could potentially provoke an immune response or interfere with host mRNAs, lncRNAs, circRNAs and RNA binding proteins. In Zika genome we identified several highly conserved regions targetable by only 20 siRNAs. In particular, only a few siRNAs survived highly stringent criteria for siRNA safety. Notably, two of our candidate siRNAs have been successfully used against other flaviviruses like Zika, both in in vitro and in vivo models. Since they were effective against two different flaviviruses, by targeting a highly conserved region, it is reasonable to hypothesize that they could be active also against Zika. Therefore, we encourage researchers to experimentally validate these promising siRNAs.
DOI: 10.1016/j.virusres.2018.07.010
PubMed: 30031046
Affiliations:
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Le document en format XML
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Giulietti</name><affiliation wicri:level="1"><nlm:affiliation>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131, Italy. Electronic address: m.giulietti@univpm.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131</wicri:regionArea><wicri:noRegion>60131</wicri:noRegion></affiliation></author><author><name sortKey="Righetti, A" sort="Righetti, A" uniqKey="Righetti A" first="A" last="Righetti">A. Righetti</name><affiliation wicri:level="1"><nlm:affiliation>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131, Italy. Electronic address: righetti@pm.univpm.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131</wicri:regionArea><wicri:noRegion>60131</wicri:noRegion></affiliation></author><author><name sortKey="Cianfruglia, L" sort="Cianfruglia, L" uniqKey="Cianfruglia L" first="L" last="Cianfruglia">L. Cianfruglia</name><affiliation wicri:level="1"><nlm:affiliation>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131, Italy. Electronic address: l.cianfruglia@univpm.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131</wicri:regionArea><wicri:noRegion>60131</wicri:noRegion></affiliation></author><author><name sortKey="Sabanovi, B" sort="Sabanovi, B" uniqKey="Sabanovi B" first="B" last="Šabanovi">B. Šabanovi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, 60131, Italy. Electronic address: sabanovic.b@gmail.com.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, 60131</wicri:regionArea><wicri:noRegion>60131</wicri:noRegion></affiliation></author><author><name sortKey="Armeni, T" sort="Armeni, T" uniqKey="Armeni T" first="T" last="Armeni">T. Armeni</name><affiliation wicri:level="1"><nlm:affiliation>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131, Italy. Electronic address: t.armeni@univpm.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131</wicri:regionArea><wicri:noRegion>60131</wicri:noRegion></affiliation></author><author><name sortKey="Principato, G" sort="Principato, G" uniqKey="Principato G" first="G" last="Principato">G. Principato</name><affiliation wicri:level="1"><nlm:affiliation>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131, Italy. Electronic address: g.b.principato@univpm.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131</wicri:regionArea><wicri:noRegion>60131</wicri:noRegion></affiliation></author><author><name sortKey="Piva, F" sort="Piva, F" uniqKey="Piva F" first="F" last="Piva">F. Piva</name><affiliation wicri:level="1"><nlm:affiliation>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131, Italy. Electronic address: f.piva@univpm.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, 60131</wicri:regionArea><wicri:noRegion>60131</wicri:noRegion></affiliation></author></analytic><series><title level="j">Virus research</title><idno type="eISSN">1872-7492</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (pharmacology)</term><term>Antiviral Agents (therapeutic use)</term><term>Computational Biology</term><term>Genome, Viral</term><term>Humans</term><term>Molecular Targeted Therapy</term><term>RNA, Small Interfering (genetics)</term><term>RNA, Small Interfering (pharmacology)</term><term>RNA, Small Interfering (therapeutic use)</term><term>RNAi Therapeutics</term><term>Safety</term><term>Virus Replication (drug effects)</term><term>Zika Virus (drug effects)</term><term>Zika Virus (genetics)</term><term>Zika Virus (physiology)</term><term>Zika Virus Infection (therapy)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antiviraux (pharmacologie)</term><term>Antiviraux (usage thérapeutique)</term><term>Biologie informatique</term><term>Génome viral</term><term>Humains</term><term>Infection par le virus Zika ()</term><term>Petit ARN interférent (génétique)</term><term>Petit ARN interférent (pharmacologie)</term><term>Petit ARN interférent (usage thérapeutique)</term><term>Réplication virale ()</term><term>Sécurité</term><term>Thérapie moléculaire ciblée</term><term>Thérapie par l'interférence par ARN</term><term>Virus Zika ()</term><term>Virus Zika (génétique)</term><term>Virus Zika (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Small Interfering</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>RNA, Small Interfering</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>RNA, Small Interfering</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Virus Replication</term><term>Zika Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Zika Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Petit ARN interférent</term><term>Virus Zika</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Petit ARN interférent</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus Zika</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Zika Virus</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Zika Virus Infection</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antiviraux</term><term>Petit ARN interférent</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Computational Biology</term><term>Genome, Viral</term><term>Humans</term><term>Molecular Targeted Therapy</term><term>RNAi Therapeutics</term><term>Safety</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Biologie informatique</term><term>Génome viral</term><term>Humains</term><term>Infection par le virus Zika</term><term>Réplication virale</term><term>Sécurité</term><term>Thérapie moléculaire ciblée</term><term>Thérapie par l'interférence par ARN</term><term>Virus Zika</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Zika virus infection is associated with the development of severe neurological disorders in adults and newborns. Although at the moment Zika virus outbreak is not threatening to become again an emergency, infection cases are still being sporadically reported and there is still no effective therapy available. A possible treatment to suppress Zika replication is represented by short interfering RNAs (siRNAs), since they have been successfully used even against Ebola, H5N1 and SARS viruses and clinical trials of siRNA-based drugs are ongoing. In order to speed up the time consuming experimental validation of effective siRNAs, we have performed a comprehensive bioinformatic analysis to design only a few promising siRNAs against Zika virus. Besides siRNA efficacy, we paid attention to broad-spectrum antiviral activity, obtained by analysing all known Zika genomes, and siRNA safety, by excluding siRNAs that could potentially provoke an immune response or interfere with host mRNAs, lncRNAs, circRNAs and RNA binding proteins. In Zika genome we identified several highly conserved regions targetable by only 20 siRNAs. In particular, only a few siRNAs survived highly stringent criteria for siRNA safety. Notably, two of our candidate siRNAs have been successfully used against other flaviviruses like Zika, both in in vitro and in vivo models. Since they were effective against two different flaviviruses, by targeting a highly conserved region, it is reasonable to hypothesize that they could be active also against Zika. Therefore, we encourage researchers to experimentally validate these promising siRNAs.</div></front></TEI><affiliations><list><country><li>Italie</li></country></list><tree><country name="Italie"><noRegion><name sortKey="Giulietti, M" sort="Giulietti, M" uniqKey="Giulietti M" first="M" last="Giulietti">M. Giulietti</name></noRegion><name sortKey="Armeni, T" sort="Armeni, T" uniqKey="Armeni T" first="T" last="Armeni">T. Armeni</name><name sortKey="Cianfruglia, L" sort="Cianfruglia, L" uniqKey="Cianfruglia L" first="L" last="Cianfruglia">L. Cianfruglia</name><name sortKey="Piva, F" sort="Piva, F" uniqKey="Piva F" first="F" last="Piva">F. Piva</name><name sortKey="Principato, G" sort="Principato, G" uniqKey="Principato G" first="G" last="Principato">G. Principato</name><name sortKey="Righetti, A" sort="Righetti, A" uniqKey="Righetti A" first="A" last="Righetti">A. Righetti</name><name sortKey="Sabanovi, B" sort="Sabanovi, B" uniqKey="Sabanovi B" first="B" last="Šabanovi">B. Šabanovi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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