Pharmacophoric characteristics of dengue virus NS2B/NS3pro inhibitors: a systematic review of the most promising compounds
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Dengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease due to the lack of specific immunotherapies and antiviral drugs. That said, the DENV NS2B/NS3pro protease complex is essential in both the viral multiplication cycle and in disease pathogenesis, and is considered a promising target for new antiviral therapies. Here, we performed a systematic review to evaluate the pharmacophoric characteristics of promising compounds against NS2B/NS3pro reported in the past 10 years. Online searches in the PUBMED/MEDLINE and SCOPUS databases resulted in 165 articles. Eight studies, which evaluated 3,384,268 molecules exhibiting protease inhibition activity, were included in this review. These studies evaluated anti-dengue activity in vitro and the IC50 and EC50 values were provided. Most compounds exhibited non-competitive inhibition. Cytotoxicity was evaluated in BHK-21, Vero, and LLC-MK2 cells, and the CC50 values obtained ranged from < 1.0 to 780.5 µM. Several groups were associated with biological activity against dengue, including nitro, catechol, halogen and ammonium quaternaries. Thus, these groups seem to be potential pharmacophores that can be further investigated to treat dengue infections.
W.G.L and C.A.L are grateful to FAPEMIG for master’s degree fellowship.
Compliance with ethical standards
This study was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (UNIVERSAL 446997/2014-5 and 449984/2014-1) and Fundação de Amparo a Pesquisa de Minas Gerais (FAPEMIG) (EDITAL APQ-00557-14).
Conflict of interest
All authors report that they do not have any conflicts of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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