Advances in drug discovery of flavivirus NS2B-NS3pro serine protease inhibitors for the treatment of Dengue, Zika, and West Nile viruses.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Emílio Emílio João, Juliana Romano Lopes, Bruna Fernanda Rodrigues Guedes, Paulo Ricardo da Silva Sanches, Chung Man Chin, Jean Leandro Dos Santos, Cauê Benito Scarim
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引用次数: 0

Abstract

Flaviviruses are vector-borne RNA viruses that seriously threaten global public health due to their high transmission index in humans, mainly in endemic areas. They spread infectious diseases that affect approximately 400 million people globally, primarily in developing countries struggling with persistent epidemic diseases. Viral infections manifest as hemorrhagic fever, encephalitis, congenital abnormalities, and fatalities. Despite nearly two decades of drug discovery campaigns, researchers have not identified promising lead compounds for clinical trials to treat or prevent flavivirus infections. Although scientists have made substantial progress through drug discovery approaches and vaccine development, resolving this complex issue might need some time. New therapeutic agents that can safely and effectively target key components of flaviviruses need to be identified. NS2B-NS3pro is an extensively studied pharmacological target among viral proteases. It plays a key role in the viral replication cycle by cleaving the polyprotein of flaviviruses and triggering the formation of structural and non-structural proteins. In this review, studies published from 2014 to 2023 were examined, and the specificity profile of compounds targeting NS2B-NS3 pro proteases for treating flavivirus infections was focused on. Additionally, the latest advancements in clinical trials were discussed. This article might provide information on the prospects of this promising pharmacological target.

用于治疗登革热、寨卡和西尼罗河病毒的黄病毒 NS2B-NS3pro 丝氨酸蛋白酶抑制剂的药物发现进展。
黄病毒是病媒传播的 RNA 病毒,由于其在人类(主要是在地方病流行地区)的传播指数很高,严重威胁着全球公共卫生。它们传播的传染病影响着全球约 4 亿人,主要是在与顽固流行病作斗争的发展中国家。病毒感染表现为出血热、脑炎、先天畸形和死亡。尽管开展了近二十年的药物研发活动,但研究人员仍未发现有希望用于临床试验的先导化合物,以治疗或预防黄病毒感染。尽管科学家们通过药物发现方法和疫苗开发取得了重大进展,但解决这一复杂问题可能还需要一些时间。需要找到能够安全有效地针对黄病毒关键成分的新治疗药物。在病毒蛋白酶中,NS2B-NS3pro 是一个被广泛研究的药理学靶点。它通过裂解黄病毒的多聚蛋白并引发结构蛋白和非结构蛋白的形成,在病毒复制周期中发挥着关键作用。本综述对 2014 年至 2023 年期间发表的研究进行了审查,重点研究了靶向 NS2B-NS3 蛋白酶的化合物治疗黄病毒感染的特异性概况。此外,还讨论了临床试验的最新进展。本文可为这一前景广阔的药理学靶点提供相关信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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