Estrategia para bloquear la entrada del virus de la Hepatitis C (HCV) en hepatocitos primarios

En esta memoria se presenta una propuesta para desarrollar un proyecto de investigación que permita establecer la eficacia de una estrategia original para evitar la entrada del virus de la hepatitis C (HCV) en las células hepáticas. Se propone la utilización combinada de dos anticuerpos contra dos factores esenciales para la entrada HCV en las células hepáticas, como son las moléculas CD81 y SR-BI. La eficacia para reducir la capacidad infectiva del HCV de bloquear individualmente cada una de estas moléculas ha sido previamente demostrada, así que en este proyecto proponemos que un uso combinado de moléculas que bloqueen ambos receptores permitiría avanzar en la búsqueda de vacunas que eviten eficazmente la infección del HCV.

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2(nd) generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.

Diseño de un vector no viral basado en nanopartículas lipídicas para el tratamiento de la hepatitis C mediante ARN de interferencia

199 p.