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

Eur J Med Chem. 2021 Jul 13;224:113698. doi: 10.1016/j.ejmech.2021.113698. Online ahead of print.ABSTRACTOver 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.PMID:34274831 | DOI:10.1016/j.ejmech.2021.113698

Source: European Journal of Medicinal Chemistry - July 18, 2021 Category: Chemistry Authors: Igor Jos é Dos Santos Nascimento Paulo Fernando da Silva Santos-J únior Thiago Mendon ça de Aquino Jo ão Xavier de Araújo-Júnior Edeildo Ferreira da Silva-J únior Source Type: research