摘要
登革热是最古老和最流行的蚊媒疾病,由来自黄病毒科的登革热病毒 (DENV) 引起。它每年感染大约 4 亿人,全球大约一半的人口居住在高风险地区。归因于登革热地理扩张的因素包括城市化、人口密度、现代交通方式、国际旅行、习惯改变、气候变化、病毒遗传学、媒介能力和媒介控制不力。尽管过去在对抗登革热方面取得了重大进展,但目前还没有有效的抗病毒疗法。在由 DENV 基因组编码的结构和非结构蛋白中,NS2B-NS3 蛋白酶复合物因其在病毒生命周期中的多重作用而成为开发抗病毒疗法的广泛研究的靶标之一。此外,发现蛋白酶抑制剂在丙型肝炎病毒 (HCV) 和人类免疫缺陷病毒 (HIV) 中是成功的。同样,几种肽、肽衍生/肽模拟物和小分子抑制剂已被鉴定为 DENV 蛋白酶抑制剂。不幸的是,它们都没有产生临床批准的药物。考虑到上述所有事实,本综述描述性地解释了 DENV 蛋白酶的分子机制和治疗潜力,以及针对 DENV 蛋白酶报道的各种竞争性抑制剂的最新信息。这篇综述可能有助于该领域的研究人员了解 DENV 蛋白酶的关键方面,这将有助于他们开发有效的新型 DENV 抑制剂,以保护全球数百万人的生命。
关键词: 登革热、DENV、抑制剂、肽、拟肽、蛋白酶、小分子。
Current Medicinal Chemistry
Title:Exploiting Dengue Virus Protease as a Therapeutic Target: Current Status, Challenges and Future Avenues
Volume: 28 Issue: 37
关键词: 登革热、DENV、抑制剂、肽、拟肽、蛋白酶、小分子。
摘要: Dengue, the oldest and the most prevalent mosquito-borne illness, is caused by the dengue virus (DENV), from the family of Flaviviridae. It infects approximately 400 million individuals per annum, with approximately half of the global population residing in high-risk areas. The factors attributed to the geographic expansion of dengue, include urbanization, population density, modern means of transportation, international travels, habit modification, climate change, virus genetics, vector capacity, and poor vector control. Despite the significant progress made in the past against dengue, no effective antiviral therapy is currently available. Among the structural and non-structural proteins encoded by DENV genome, the NS2B−NS3 protease complex is amongst the extensively studied targets for the development of antiviral therapeutics owing to its multiple roles in virus life cycle. Furthermore, protease inhibitors were found to be successful in Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Likewise, several peptidic, peptide derived/peptidomimetic, and small molecules inhibitors have been identified as DENV protease inhibitors. Unfortunately, none of them have resulted in a clinically approved drug. Considering all the abovementioned facts, this review descriptively explains the molecular mechanism and therapeutic potential of DENV protease along with an up to date information on various competitive inhibitors reported against DENV protease. This review might be helpful for the researchers working in this area to understand the critical aspects of DENV protease that will help them develop effective and novel inhibitors against DENV to protect lives of millions of people worldwide.
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Cite this article as:
Exploiting Dengue Virus Protease as a Therapeutic Target: Current Status, Challenges and Future Avenues, Current Medicinal Chemistry 2021; 28 (37) . https://dx.doi.org/10.2174/0929867328666210629152929
DOI https://dx.doi.org/10.2174/0929867328666210629152929 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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