Potential for Protein Kinase Pharmacological Regulation in Flaviviridae Infections

17 Pág.Protein kinases (PKs) are enzymes that catalyze the transfer of the terminal phosphate group from ATP to a protein acceptor, mainly to serine, threonine, and tyrosine residues. PK catalyzed phosphorylation is critical to the regulation of cellular signaling pathways that affect crucial cell processes, such as growth, differentiation, and metabolism. PKs represent attractive targets for drugs against a wide spectrum of diseases, including viral infections. Two different approaches are being applied in the search for antivirals: compounds directed against viral targets (direct-acting antivirals, DAAs), or against cellular components essential for the viral life cycle (host-directed antivirals, HDAs). One of the main drawbacks of DAAs is the rapid emergence of drug-resistant viruses. In contrast, HDAs present a higher barrier to resistance development. This work reviews the use of chemicals that target cellular PKs as HDAs against virus of the Flaviviridae family (Flavivirus and Hepacivirus), thus being potentially valuable therapeutic targets in the control of these pathogens.This research was partially funded by Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, (INIA) grants RTA-2015-00009-00-00 and E-RTA-2017-00003-C02-01, and Comunidad Autónoma de Madrid grant S2018/BAA-4370 (PLATESA2-CM).Peer reviewe