Padmapriya P, Gracy Fathima S, Ramanathan Giriprasath, V Yuvaraj, A Khaleefathullah Sheriff, Kaveri K, Gunasekaran P, Tirichurapalli Sivagnanam Uma, Thennarasu Sathiah
Biological Material Lab, CSIR-Central Leather Research Institute, Adyar, Chennai, India.
Department of Virology, King Institute of Preventive Medicine and Research, Guindy, Chennai, 600032, Tamilnadu, India.
Acta Trop. 2018 Dec;188:1-8. doi: 10.1016/j.actatropica.2018.08.022. Epub 2018 Aug 23.
Dengue fever is a severe, widespread disease with more than 2 million diagnosed infections per year. The Dengue virus protease represents a cardinal target for prudent drug design. Among the four serotypes Dengue 2 is known for the occurrence of its frequent epidemics. The new compound inhibited the Dengue-2 in the low-micromolar range in cells. At the moment, protease inhibitors are not actively tried against dengue virus as therapeutic option. We have identified thiosemicarbazones derived phenyl-acetyl ketones as candidate for a novel class of protease inhibitors. Here, we report the selective and non-competitive inhibition of the Dengue virus serotype 2 in vitro and in silico. Molecular docking suggests binding at a specific active site. In addition to the docking assays, few techniques were developed to interpret these molecules's antiviral profile in vitro.
登革热是一种严重的、广泛传播的疾病,每年有超过200万例确诊感染病例。登革热病毒蛋白酶是合理药物设计的主要靶点。在四种血清型中,登革热2型以频繁发生流行而闻名。这种新化合物在细胞中以低微摩尔浓度范围抑制登革热2型。目前,蛋白酶抑制剂尚未作为治疗选择积极用于对抗登革热病毒。我们已经确定硫代氨基脲衍生的苯乙酰酮作为新型蛋白酶抑制剂类别的候选物。在此,我们报告登革热病毒2型在体外和计算机模拟中的选择性和非竞争性抑制作用。分子对接表明其在特定活性位点结合。除了对接试验外,还开发了一些技术来解释这些分子在体外的抗病毒谱。