Dansana Jarmani, Purohit Priyanka, Panda Madhusmita, Meher Biswa Ranjan
Computational Biology and Bioinformatics Laboratory, PG Department of Botany, Berhampur University, Berhampur, Odisha, 760007, India.
Computational Biology and Bioinformatics Laboratory, PG Department of Botany, Berhampur University, Berhampur, Odisha, 760007, India.
Phytomedicine. 2025 Jan;136:156359. doi: 10.1016/j.phymed.2024.156359. Epub 2024 Dec 29.
The mosquito-borne pathogenic alphavirus known as Chikungunya virus (CHIKV) is becoming a greater hazard to public health, which causes thousands of cases annually in both rural and urban areas of many different nations throughout the world. Finding and creating new leads for the CHIKV virus is crucial because there are currently no effective medications or vaccinations against it. The non-structural protein 2 (nsP2) protease has emerged as a promising target for therapeutic intervention due to its crucial role in viral replication.
This systematic review aims to evaluate recent advances in natural products as inhibitors of the CHIKV nsP2 protease, summarizing current research, identifying promising compounds, and highlighting gaps in the existing knowledge.
A comprehensive literature search was conducted between January 2006, and June 2024 using databases including PubMed, Scopus, Science Direct, and Google Scholar. Search terms included CHIKV, nsP2 protease, antivirals, natural products, phytochemicals, and inhibitors. Studies were selected based on predefined inclusion and exclusion criteria, focusing on original research articles examining natural products as inhibitors of CHIKV nsP2 protease.
Relevant studies were screened, and data were extracted regarding the source of natural compounds, methods of extraction, chemical structures, mechanisms of action, potency, and efficacy in inhibiting nsP2 protease or CHIKV replication.
The review included 40 studies, revealing a variety of natural products and their derivatives with inhibitory effects on CHIKV nsP2 protease. Several compounds demonstrated promising inhibitory activity with EC50 values in the micromolar range. Mechanistic studies revealed diverse modes of action, including inhibition of protease activity or interference with viral replication processes.
Natural products have gained attention for their diverse chemical structures and bioactivities, offering a rich source of compounds with antiviral potential. We summarize the current knowledge on natural products derived from various sources including flavonoids, alkaloids, terpenoids, polyphenols, and some derivative compounds that have demonstrated inhibitory effects against CHIKV through different mechanisms of action. Overall, this systematic review underscores the importance of exploring natural products as promising candidates for the development of effective therapeutics against Chikungunya fever, particularly through targeting the nsP2 protease.
名为基孔肯雅病毒（CHIKV）的蚊媒致病性甲病毒对公众健康构成了越来越大的威胁，在世界上许多不同国家的农村和城市地区，每年都会导致数千例病例。由于目前没有针对CHIKV病毒的有效药物或疫苗，寻找并开发针对该病毒的新线索至关重要。非结构蛋白2（nsP2）蛋白酶因其在病毒复制中的关键作用，已成为治疗干预的一个有前景的靶点。
本系统评价旨在评估天然产物作为CHIKV nsP2蛋白酶抑制剂的最新进展，总结当前研究，确定有前景的化合物，并突出现有知识中的空白。
2006年1月至2024年6月期间，使用包括PubMed、Scopus、Science Direct和谷歌学术在内的数据库进行了全面的文献检索。检索词包括CHIKV、nsP2蛋白酶、抗病毒药物、天然产物、植物化学物质和抑制剂。根据预先定义的纳入和排除标准选择研究，重点关注将天然产物作为CHIKV nsP2蛋白酶抑制剂进行研究的原创性研究文章。
筛选相关研究，并提取有关天然化合物来源、提取方法、化学结构、作用机制、效力以及抑制nsP2蛋白酶或CHIKV复制的功效的数据。
该评价纳入了40项研究，揭示了多种对CHIKV nsP2蛋白酶具有抑制作用的天然产物及其衍生物。几种化合物表现出有前景的抑制活性，半数有效浓度（EC50）值在微摩尔范围内。机制研究揭示了多种作用模式，包括抑制蛋白酶活性或干扰病毒复制过程。
天然产物因其多样的化学结构和生物活性而受到关注，为具有抗病毒潜力的化合物提供了丰富的来源。我们总结了目前关于来自各种来源的天然产物的知识，包括黄酮类化合物、生物碱、萜类化合物、多酚以及一些通过不同作用机制对CHIKV具有抑制作用的衍生物。总体而言，本系统评价强调了探索天然产物作为开发针对基孔肯雅热的有效治疗方法的有前景候选物的重要性，特别是通过靶向nsP2蛋白酶。
