Actividad antiviral de tiosemicarbazonas y N4-ariltiosemicarbazonas derivadas de 1-indanonas frente a BVDV

Bovine viral diarrhea virus (BVDV) is a major pathogen of cattle with a great economic impact. The identification of antivirals for the treatment of BVDV infections and outbreak control is relevant. After drug-modulation of 5,6-TSC, a compound previously identified as a non-nucleoside inhibitor (NNI...

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Detalles Bibliográficos
Autor principal: Fabiani, Matias
Otros Autores: Castro, Eliana
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2020
Materias:
BVDV
Tiosemicarbozonas
N4-ariltiosemicarbazonas
1-indanona
Ciencias de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_6335
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6335.dir/6335.PDF
Aporte de:
Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Bovine viral diarrhea virus (BVDV) is a major pathogen of cattle with a great economic impact. The identification of antivirals for the treatment of BVDV infections and outbreak control is relevant. After drug-modulation of 5,6-TSC, a compound previously identified as a non-nucleoside inhibitor (NNI) of BVDV RNA-polymerase (RdRp), a series of thiosemicarbazones (TSC) and N4-arylthiosemicarbazones derived from 1-indanones was synthesized. Two compounds with higher anti-BVDV activity were identified: N4-(p-nitrophenyl)-TSC derived from 5,6-dimethoxy-1-indanone (N4-TSC) and TSC derived from 6-nitro-1-indanone (6NO2-TSC), which were active against BVDV strains from different genotypes and biotypes and inactive against other RNA viruses. It was demonstrated that these compounds act in intermediate stages of the viral replication cycle. Particularly, N4-TSC acts by blocking viral RNA synthesis, and by means of BVDV resistance selection (N4-TSCR), viral RdRp was identified as the molecular target. Docking and molecular dynamics studies showed that the mutations N264D and A392E, found in N4-TSCR viruses, alter the interactions of N4-TSC with RdRp and are responsible for antiviral resistance.

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