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 p...
| Autores: | , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Recursos: | Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| Repositorio: | r-FISABIO. Repositorio Institucional de Producción Científica |
| OAI Identifier: | oai:fisabio.fundanetsuite.com:p4928 |
| Acesso em linha: | https://fisabio.portalinvestigacion.com/publicaciones/4928 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055231142&doi=10.2147%2fDDDT.S171087&partnerID=40&md5=f373b5d3f8e480de6e616b8dbbb3021b |
| Access Level: | acceso abierto |
| Palavra-chave: | IPNV HCV antiviral drugs non-nucleoside inhibitors RdRp molecular docking |
| Resumo: | 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 mu M range with different activity depending on the IPNV strain used. |
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