Recent advances in the development of methyltransferase (MTase) inhibitors against (re)emerging arboviruses diseases dengue and Zika.

Timoteo Delgado-Maldonado, Antonio Moreno-Herrera, Gerard Pujadas, Lenci K Vázquez-Jiménez, Alonzo González-González, Gildardo Rivera

Journal: European journal of medicinal chemistry 2023;252():115290

PMID: 36958266

Abstract

Emerging and/or re-emerging viral diseases such as dengue and Zika are a worldwide concern. Therefore, new antiviral therapeutics are necessary. In this sense, a non-structural protein with methyltransferase (MTase) activity is an attractive drug target because it plays a crucial role in dengue and Zika virus replication. Different drug strategies such as virtual screening, molecular docking, and molecular dynamics have identified new inhibitors that bind on the MTase active site. Therefore, in this review, we analyze MTase inhibitors, including S-adenosyl-L-methionine (SAM), S-adenosyl-l-homocysteine (SAH) and guanosine-5'-triphosphate (GTP) analogs, nitrogen-containing heterocycles (pyrimidine, adenosine, and pyridine), urea derivatives, and natural products. Advances in the design of MTase inhibitors could lead to the optimization of a possible single or broad-spectrum antiviral drug against dengue and Zika virus.

Copyright © 2023 Elsevier Masson SAS. All rights reserved.

Address: Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, Mexico.; Departament de Bioquímica i Biotecnologia, Research group in Cheminformatics & Nutrition, Campus de Sescelades, Universitat Rovira i Virgili, 43007, Tarragona, Catalonia, Spain.; Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, Mexico. Electronic address: [email protected].

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