Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi, 75720, Pakistan.
Curr Med Chem. 2024;31(16):2195-2233. doi: 10.2174/0929867331666230918110144.
Viral infections continue to increase morbidity and mortality severely. The flavivirus genus has fifty different species, including the dengue, Zika, and West Nile viruses that can infect 40% of individuals globally, who reside in at least a hundred different countries. Dengue, one of the oldest and most dangerous human infections, was initially documented by the Chinese Medical Encyclopedia in the Jin period. It was referred to as "water poison," connected to flying insects, . DENV causes some medical expressions like dengue hemorrhagic fever, acute febrile illness, and dengue shock syndrome.
According to the World Health Organization report of 2012, 2500 million people are in danger of contracting dengue fever worldwide. According to a recent study, 96 million of the 390 million dengue infections yearly show some clinical or subclinical severity. There is no antiviral drug or vaccine to treat this severe infection. It can be controlled by getting enough rest, drinking plenty of water, and using painkillers. The first dengue vaccine created by Sanofi, called Dengvaxia, was previously approved by the USFDA in 2019. All four serotypes of the DENV1-4 have shown re-infection in vaccine recipients. However, the usage of Dengvaxia has been constrained by its adverse effects.
Different classes of compounds have been reported against DENV, such as nitrogen-containing heterocycles (i.e., imidazole, pyridine, triazoles quinazolines, quinoline, and indole), oxygen-containing heterocycles (i.e., coumarins), and some are mixed heterocyclic compounds of S, N (thiazole, benzothiazine, and thiazolidinediones), and N, O (i.e., oxadiazole). There have been reports of computationally designed compounds to impede the molecular functions of specific structural and non-structural proteins as potential therapeutic targets. This review summarized the current progress in developing dengue protease inhibitors.
病毒感染继续严重地增加发病率和死亡率。黄病毒属有五十种不同的物种，包括登革热、寨卡和西尼罗河病毒，这些病毒可以感染全球 40%的人，这些人居住在至少 100 个不同的国家。登革热是最古老和最危险的人类感染之一，最初由中国医学百科全书在金时期记录。它被称为“水毒”，与飞虫有关。登革热病毒引起一些医学表现，如登革出血热、急性发热性疾病和登革热休克综合征。
根据世界卫生组织 2012 年的报告，全世界有 2.5 亿人面临感染登革热的危险。根据最近的一项研究，每年 3.9 亿例登革热感染中有 9600 万例表现出某种临床或亚临床严重程度。目前尚无治疗这种严重感染的抗病毒药物或疫苗。可以通过充分休息、多喝水和使用止痛药来控制。赛诺菲公司制造的第一种登革热疫苗，称为 Dengvaxia，此前于 2019 年获得美国食品和药物管理局的批准。DENV1-4 的所有四个血清型在疫苗接种者中都显示出再次感染。然而，由于其副作用，Dengvaxia 的使用受到限制。
已经报道了针对 DENV 的不同类别的化合物，如含氮杂环（如咪唑、吡啶、三唑、喹唑啉、喹啉和吲哚）、含氧杂环（如香豆素）以及一些 S、N（噻唑、苯并噻嗪和噻唑烷二酮）和 N、O（即，噁二唑）混合杂环化合物。已经有报道称，计算设计的化合物可以阻止特定结构和非结构蛋白的分子功能，作为潜在的治疗靶点。这篇综述总结了开发登革热蛋白酶抑制剂的最新进展。
