Bithiazole inhibitors of PI4KB show broad-spectrum antiviral activity against different viral families.

Autor: Martina MG; Dipartimento di Scienze Degli Alimenti e Del Farmaco (DipALIFAR), Università Degli Studi di Parma, Viale Delle Scienze, 27/A, 43124, Parma, Italy., Carlen V; Institute of Microbiology, University Hospital of Lausanne, University of Lausanne, 1011, Lausanne, Switzerland., Van der Reysen S; Dipartimento di Scienze Degli Alimenti e Del Farmaco (DipALIFAR), Università Degli Studi di Parma, Viale Delle Scienze, 27/A, 43124, Parma, Italy., Bianchi E; Istituto di Genetica Molecolare, IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, 27100, Pavia, Italy., Cabella N; Istituto di Genetica Molecolare, IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, 27100, Pavia, Italy., Crespan E; Istituto di Genetica Molecolare, IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, 27100, Pavia, Italy., Radi M; Dipartimento di Scienze Degli Alimenti e Del Farmaco (DipALIFAR), Università Degli Studi di Parma, Viale Delle Scienze, 27/A, 43124, Parma, Italy. Electronic address: marco.radi@unipr.it., Cagno V; Institute of Microbiology, University Hospital of Lausanne, University of Lausanne, 1011, Lausanne, Switzerland. Electronic address: valeria.cagno@chuv.ch.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2024 Nov; Vol. 231, pp. 106003. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1016/j.antiviral.2024.106003
Abstrakt: Broad-spectrum antivirals can be extremely important for pandemic preparedness. Targeting host factors dispensable for the host but indispensable for the virus can result in high barrier to resistance and a large range of viruses targeted. PI4KB is a lipid kinase involved in the replication of several RNA viruses, but common inhibitors of this target are mainly active against members of the Picornaviridae family. Herein we describe the optimization of bithiazole PI4KB inhibitors as broad-spectrum antivirals (BSAs) active against different members of the Picornaviridae, Coronaviridae, Flaviviridae and Poxviridae families. Since some of these viruses are transmitted via respiratory route, the efficacy of one of the most promising compounds was evaluated in an airway model. The molecule showed complete viral inhibition and absence of toxicity. These results pave the road for the development of new BSAs.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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