Pharmacophoric characteristics of dengue virus NS2B/NS3pro inhibitors: a systematic review of the most promising compounds

• Published in: Archives of virology Vol. 163; no. 3; pp. 575 - 586
• Main Authors: Leonel, Camyla Alves, Lima, William Gustavo, dos Santos, Michelli, Ferraz, Ariane Coelho, Taranto, Alex Gutterres, de Magalhães, José Carlos, dos Santos, Luciana Lara, Ferreira, Jaqueline Maria Siqueira
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.03.2018; Springer Nature B.V
• Subjects: Ammonium; Antiviral agents; Biological activity; Biomedical and Life Sciences; Biomedicine; Catechol; Cytotoxicity; Dengue fever; Hemorrhage; Immunotherapy; Infectious Diseases; Medical Microbiology; Pharmacophores; Proteinase; Review; Reviews; Systematic review; Virology
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-017-3641-5

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 IC 50 and EC 50 values were provided. Most compounds exhibited non-competitive inhibition. Cytotoxicity was evaluated in BHK-21, Vero, and LLC-MK2 cells, and the CC 50 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.