非化学修饰的药物靶点发现技术在中药研究中的应用

中医药是我国的科学与文化瑰宝，具有数千年的临床用药经验。中医药在复杂疾病及慢性疾病防治方面具有显著优势，在当前全球肆虐的新型冠状病毒肺炎（corona virus disease 2019，COVID-19）防治中也彰显了其优势，但由于作用机制不清楚等问题严重限制了其推广应用。化学药治疗疾病作用机制明确，具有成熟的药物靶点发现技术，主要包括化学修饰技术和非化学修饰技术。中药具有多成分、多靶点的作用特点，应用化学修饰技术进行作用靶点的研究具有一定的局限性。因此，主要介绍细胞热位移分析、分子对接技术、药物亲和反应的靶点稳定性和表面等离子共振技术等非化学修饰的药物靶点发现技术的原理、操作流程和应用，并对其在中药作用机制研究中的潜在优势与不足进行讨论，以期探索出一种中药作用靶点发现模式，为中药作用机制的阐明提供参考与借鉴，助推中医药现代化进程。

Application of non-chemical modification drug target discovery techniques in traditional Chinese medicine

Traditional Chinese medicine (TCM) is a science and cultural treasure of our country, with thousands of years of clinical experience in medication. TCM has significant advantages in prevention and treatment of complex diseases and chronic diseases, and has also demonstrated its advantages in prevention and treatment of corona virus disease 2019 (COVID-19) that is currently raging around the world, but due to unclear mechanism problem, the promotion and application of TCM have been seriously limited. Mechanism of Western medicine is clear, and it has mature drug target discovery technology, mainly including chemical modification technology and non-chemical modification technology. Due to the characteristics of multi-component, multi-target action of TCM, the application of chemical modification technology in TCM mechanism study has certain limitations. Thus, the principle, operation steps and application of non-chemically modified drug target technology such as cellular thermal shift assay, molecular docking, drug affinity responsive target stability, surface plasmon resonance are introduced in this paper. The potential advantages and disadvantages of such non-chemically modified drug target technologies are discussed in the study on mechanism of TCM, in order to explore a target discovery model of TCM target discovery, provide reference for elucidating the mechanism of TCM, and promote the modernization process of TCM.