Jadav Surender Singh, Sinha Barij Nayan, Hilgenfeld Rolf, Jayaprakash Venkatesan
Department of Pharmaceutical Sciences & Technology, Birla Insitute of Technology, Mesra, Ranchi, Jharkhand, India.
Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, 23538 Lübeck, Germany.
Curr Comput Aided Drug Des. 2017 Nov 10;13(4):346-361. doi: 10.2174/1573409913666170309145308.
Chikungunya is a viral infection caused by Chikungunya virus (CHIKV), an arbovirus transmitted through mosquito (Aedes aegypti and Aedes albopictus) bite. The virus from sylvatic cycle in Africa mutated to new vector adaptation and became one of the major emerging and re-emerging viral infections in the past decade, affecting more than 40 countries. Efforts are being made by many researches to develop means to prevent and control the infection through vaccines and vector control strategy. On the other hand, search for novel chemotherapeutic agents for the treatment of infected patients is on. Approach of repurposed drug is one way of identifying an existing drug for the treatment of CHIKV infection.
Review the history of CHIKV nsp2 protease inhibitors derived through structure-based computer-aided drug design along with phytochemicals identified as anti-CHIKV agents.
A survey on CHIKV inhibitors reported till date has been carriedout. The data obtained were organized and discussed under natural substances and synthetic derivatives obtained as result of rational design.
The review provides a well organized content in chronological order that has highly significant information for medicinal chemist who wish to explore the area of Anti-CHIKV drug design and development. Natural compounds with different scaffolds provides an opportunity to explore Ligand based drug design (LBDD), while rational drug design approaches provides opportunity to explore the Structure based drug design.
From the presented mini-review, readers can understand that this area is less explored and has lots of potential in anti-CHIKVviral drug design & development. of reported literature inferred that, unlike other viral proteases, the nsP2 protease can be targeted for CHIKV viral inhibition. The HTVS process for the identification of anti-CHIK agents provided a few successive validated lead compounds against CHIKV infections.
基孔肯雅热是由基孔肯雅病毒（CHIKV）引起的一种病毒感染，CHIKV是一种通过蚊子（埃及伊蚊和白纹伊蚊）叮咬传播的虫媒病毒。来自非洲野生传播周期的该病毒已变异为适应新载体，并在过去十年中成为主要的新出现和再次出现的病毒感染之一，影响了40多个国家。许多研究正在努力通过疫苗和病媒控制策略来开发预防和控制感染的方法。另一方面，正在寻找用于治疗感染患者的新型化学治疗剂。重新利用药物的方法是确定现有药物用于治疗CHIKV感染的一种方式。
回顾通过基于结构的计算机辅助药物设计获得的CHIKV非结构蛋白2（nsp2）蛋白酶抑制剂以及被鉴定为抗CHIKV药物的植物化学物质的历史。
对迄今为止报道的CHIKV抑制剂进行了一项调查。所获得的数据在通过合理设计得到的天然物质和合成衍生物下进行整理和讨论。
该综述按时间顺序提供了组织良好的内容，对于希望探索抗CHIKV药物设计和开发领域的药物化学家具有非常重要的信息。具有不同支架的天然化合物为探索基于配体的药物设计（LBDD）提供了机会，而合理药物设计方法为探索基于结构的药物设计提供了机会。
从所呈现的小型综述中，读者可以了解到该领域的探索较少，在抗CHIKV病毒药物设计和开发方面有很大潜力。已报道文献推断，与其他病毒蛋白酶不同，nsP2蛋白酶可作为CHIKV病毒抑制的靶点。用于鉴定抗CHIK药物的高通量虚拟筛选（HTVS）过程提供了一些连续验证的针对CHIKV感染的先导化合物。
