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Insights into RNA-dependent RNA Polymerase Inhibitors as Antiinfluenza Virus Agents

Author(s):

Ilaria Giacchello, Francesca Musumeci*, Ilaria D’Agostino, Chiara Greco, Giancarlo Grossi and Silvia Schenone   Pages 1 - 23 ( 23 )

Abstract:


Background: Influenza is a seasonal disease which affects millions of people every year and has a significant economic impact. Vaccines are the best strategy to fight this viral pathology, but they are not always available or administrable, prompting the search for antiviral drugs. RNA-dependent RNA polymerase (RdRp) recently emerged as a promising target, because of its key role in viral replication and its high conservation among viral strains.

Discussion: This review presents an overview of the most interesting RdRp inhibitors that have appeared in the literature since 2000. Compounds already approved or in clinical trials and a selection of inhibitors endowed with different scaffolds are described, along with the main features responsible for their activity.

Results: RdRp inhibitors are emerging as a new strategy to fight viral infections, and the importance of this class of drugs has been confirmed by the FDA approval of baloxavir marboxil in 2018. Despite the complexity of the RdRp machine makes the identification of new compounds a challenging research topic, it is likely that in the coming years this field will attract the interest of a number of academic and industrial scientists because of the potential strength of this therapeutic approach.

Keywords:

RNA-dependent RNA polymerase inhibitors, influenza A virus, protein-protein interaction inhibitors, small molecules, antiviral drugs, PA-PB1 inhibitors

Affiliation:

Department of Pharmacy, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Department of Pharmacy, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Department of Pharmacy, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Department of Pharmacy, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Department of Pharmacy, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa



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