Insights on Dengue and Zika NS5 RNA-dependent RNA polymerase (RdRp) inhibitors.

Autor: Nascimento IJDS; Chemistry and Biotechnology Institute, Federal University of Alagoas, Maceió, Brazil., Santos-Júnior PFDS; Chemistry and Biotechnology Institute, Federal University of Alagoas, Maceió, Brazil., Aquino TM; Chemistry and Biotechnology Institute, Federal University of Alagoas, Maceió, Brazil., Araújo-Júnior JX; Laboratory of Medicinal Chemistry, Pharmaceutical Sciences Institute, Federal University of Alagoas, Maceió, Brazil., Silva-Júnior EFD; Chemistry and Biotechnology Institute, Federal University of Alagoas, Maceió, Brazil. Electronic address: edeildo.junior@iqb.ufal.br.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2021 Nov 15; Vol. 224, pp. 113698. Date of Electronic Publication: 2021 Jul 13.
DOI: 10.1016/j.ejmech.2021.113698
Abstrakt: Over recent years, many outbreaks caused by (re)emerging RNA viruses have been reported worldwide, including life-threatening Flaviviruses, such as Dengue (DENV) and Zika (ZIKV). Currently, there is only one licensed vaccine against Dengue, Dengvaxia®. However, its administration is not recommended for children under nine years. Still, there are no specific inhibitors available to treat these infectious diseases. Among the flaviviral proteins, NS5 RNA-dependent RNA polymerase (RdRp) is a metalloenzyme essential for viral replication, suggesting that it is a promising macromolecular target since it has no human homolog. Nowadays, several NS5 RdRp inhibitors have been reported, while none inhibitors are currently in clinical development. In this context, this review constitutes a comprehensive work focused on RdRp inhibitors from natural, synthetic, and even repurposing sources. Furthermore, their main aspects associated with the structure-activity relationship (SAR), proposed mechanisms of action, computational studies, and other topics will be discussed in detail.
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 © 2021 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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