Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)

[Introduction], Infectious pancreatic necrosis virus (IPNV) causes serious losses in several fish species of commercial interest. IPNV is a non-enveloped double-stranded RNA virus with a genome consisting of two segments A and B. Segment B codes for the VP1 protein, a non-canonical RNA-dependent RNA...

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Autores: Bello-Pérez, Melissa, Falcó, Alberto, Galiano, V., Coll Morales, Julio, Pérez, Luis, Encinar, José Antonio
Tipo de documento: artigo
Data de publicação:2018
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/290603
Acesso em linha:http://hdl.handle.net/10261/290603
Access Level:Acceso aberto
Palavra-chave:IPNV
HCV
Antiviral drugs
Non-nucleoside inhibitors
RdRp
Molecular docking
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spelling Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)Bello-Pérez, MelissaFalcó, AlbertoGaliano, V.Coll Morales, JulioPérez, LuisEncinar, José AntonioIPNVHCVAntiviral drugsNon-nucleoside inhibitorsRdRpMolecular docking[Introduction], Infectious pancreatic necrosis virus (IPNV) causes serious losses in several fish species of commercial interest. IPNV is a non-enveloped double-stranded RNA virus with a genome consisting of two segments A and B. Segment B codes for the VP1 protein, a non-canonical RNA-dependent RNA polymerase that can be found both in its free form and linked to the end of genomic RNA, an essential enzyme for IPNV replication. [Materials and methods], We take advantage of the knowledge over the allosteric binding site described on the surface of the thumb domain of Hepatitis C virus (HCV) polymerase to design new non-nucleoside inhibitors against the IPNV VP1 polymerase. [Results], Molecular docking techniques have been used to screen a chemical library of 23,760 compounds over a defined cavity in the surface of the thumb domain. Additional ADMET (absorption, distribution, metabolism, excretion, and toxicity) filter criteria has been applied. [Conclusion], We select two sets of 9 and 50 inhibitor candidates against the polymerases of HCV and IPNV, respectively. Two non-toxic compounds have been tested in vitro with antiviral capacity against IPNV Sp and LWVRT60 strains in the low μM range with different activity depending on the IPNV strain usedPeer reviewedDove PressColl Morales, Julio [0000-0001-8496-3493]Falcó, Alberto [0000-0001-7726-6577]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/290603reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2906032026-05-22T06:33:51Z
dc.title.none.fl_str_mv Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)
title Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)
spellingShingle Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)
Bello-Pérez, Melissa
IPNV
HCV
Antiviral drugs
Non-nucleoside inhibitors
RdRp
Molecular docking
title_short Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)
title_full Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)
title_fullStr Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)
title_full_unstemmed Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)
title_sort Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic necrosis virus (IPNV)
dc.creator.none.fl_str_mv Bello-Pérez, Melissa
Falcó, Alberto
Galiano, V.
Coll Morales, Julio
Pérez, Luis
Encinar, José Antonio
author Bello-Pérez, Melissa
author_facet Bello-Pérez, Melissa
Falcó, Alberto
Galiano, V.
Coll Morales, Julio
Pérez, Luis
Encinar, José Antonio
author_role author
author2 Falcó, Alberto
Galiano, V.
Coll Morales, Julio
Pérez, Luis
Encinar, José Antonio
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Coll Morales, Julio [0000-0001-8496-3493]
Falcó, Alberto [0000-0001-7726-6577]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv IPNV
HCV
Antiviral drugs
Non-nucleoside inhibitors
RdRp
Molecular docking
topic IPNV
HCV
Antiviral drugs
Non-nucleoside inhibitors
RdRp
Molecular docking
description [Introduction], Infectious pancreatic necrosis virus (IPNV) causes serious losses in several fish species of commercial interest. IPNV is a non-enveloped double-stranded RNA virus with a genome consisting of two segments A and B. Segment B codes for the VP1 protein, a non-canonical RNA-dependent RNA polymerase that can be found both in its free form and linked to the end of genomic RNA, an essential enzyme for IPNV replication. [Materials and methods], We take advantage of the knowledge over the allosteric binding site described on the surface of the thumb domain of Hepatitis C virus (HCV) polymerase to design new non-nucleoside inhibitors against the IPNV VP1 polymerase. [Results], Molecular docking techniques have been used to screen a chemical library of 23,760 compounds over a defined cavity in the surface of the thumb domain. Additional ADMET (absorption, distribution, metabolism, excretion, and toxicity) filter criteria has been applied. [Conclusion], We select two sets of 9 and 50 inhibitor candidates against the polymerases of HCV and IPNV, respectively. Two non-toxic compounds have been tested in vitro with antiviral capacity against IPNV Sp and LWVRT60 strains in the low μM range with different activity depending on the IPNV strain used
publishDate 2018
dc.date.none.fl_str_mv 2018
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/290603
url http://hdl.handle.net/10261/290603
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Dove Press
publisher.none.fl_str_mv Dove Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,228081

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