A number of previous successful attempts in the search for therapeutics for a variety of human pathologies highlight the importance of computational technologies in the drug discovery pipeline. This approach, often referred to as computer-aided drug design, is unfortunately inapplicable when the precise information regarding the three-dimensional structure of disease-associated proteins or the mechanism by which they are altered to generate misfolded isoforms are missing. A typical example is represented by prion diseases, fatal pathologies of the nervous system characterized by the conformational conversion of a physiological protein called PrP C into a misfolded and infectious isoform referred to as PrP Sc . Missing information regarding the atomic structure of PrP Sc as well as the mechanism of templated conversion of PrP C has severely halted the discovery of effective therapies for prion diseases. In this manuscript, we review emerging opportunities to apply computer-aided techniques to target PrP C , PrP Sc or to design inhibitors of prion replication, and discuss how these fast-evolving technologies could lay the groundwork for the application of entirely novel rational drug design schemes for these devastating pathologies.

Ok google, how could i design therapeutics against prion diseases? / Rigoli, M.; Spagnolli, G.; Faccioli, P.; Requena, J. R.; Biasini, E.. - In: CURRENT OPINION IN PHARMACOLOGY. - ISSN 1471-4892. - 44:(2019), pp. 39-45. [10.1016/j.coph.2019.03.015]

Ok google, how could i design therapeutics against prion diseases?

Rigoli M.;Spagnolli G.;Faccioli P.;Biasini E.
2019-01-01

Abstract

A number of previous successful attempts in the search for therapeutics for a variety of human pathologies highlight the importance of computational technologies in the drug discovery pipeline. This approach, often referred to as computer-aided drug design, is unfortunately inapplicable when the precise information regarding the three-dimensional structure of disease-associated proteins or the mechanism by which they are altered to generate misfolded isoforms are missing. A typical example is represented by prion diseases, fatal pathologies of the nervous system characterized by the conformational conversion of a physiological protein called PrP C into a misfolded and infectious isoform referred to as PrP Sc . Missing information regarding the atomic structure of PrP Sc as well as the mechanism of templated conversion of PrP C has severely halted the discovery of effective therapies for prion diseases. In this manuscript, we review emerging opportunities to apply computer-aided techniques to target PrP C , PrP Sc or to design inhibitors of prion replication, and discuss how these fast-evolving technologies could lay the groundwork for the application of entirely novel rational drug design schemes for these devastating pathologies.
2019
M Rigoli, G Spagnolli, P Faccioli, JR Requena, E Biasini
Rigoli, M.; Spagnolli, G.; Faccioli, P.; Requena, J. R.; Biasini, E.
Ok google, how could i design therapeutics against prion diseases? / Rigoli, M.; Spagnolli, G.; Faccioli, P.; Requena, J. R.; Biasini, E.. - In: CURRENT OPINION IN PHARMACOLOGY. - ISSN 1471-4892. - 44:(2019), pp. 39-45. [10.1016/j.coph.2019.03.015]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/254953
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