摘 要
新冠病毒（SARS - CoV - 2）引发的全球公共卫生危机促使抗病毒药物研发成为关键领域。本研究旨在探讨多种抗病毒药物对新冠病毒的抑制作用及机制，以期为临床治疗提供理论依据。通过体外细胞实验，选用多种人源细胞系模拟人体环境，利用实时荧光定量PCR、Western blot等技术检测药物处理后细胞内病毒核酸与蛋白表达水平变化，并借助分子对接、分子动力学模拟分析药物与病毒关键靶点如3CLpro、RdRp等相互作用模式。结果表明，部分核苷类药物可有效抑制病毒RNA合成，非核苷类药物则主要干扰病毒蛋白功能。创新性地发现某新型化合物能特异性结合3CLpro活性位点且具有高亲和力，显著降低病毒复制能力。同时，深入探究了药物影响宿主细胞因子风暴产生的可能性，发现特定药物组合可调节免疫反应相关信号通路，减轻炎症反应。结论是多种抗病毒药物从不同环节发挥抑制新冠病毒的作用，新型化合物为抗新冠药物研发提供了新方向，药物组合疗法有助于改善患者预后，减少并发症发生。
关键词：新冠病毒抑制；抗病毒药物；3CLpro
Abstract
The global public health crisis caused by SARS-CoV-2 has underscored the critical importance of antiviral drug development. This study aims to investigate the inhibitory effects and mechanisms of various antiviral drugs on SARS-CoV-2, providing theoretical support for clinical treatment. Through in vitro cell experiments using multiple human cell lines to mimic the human environment, we employed techniques such as real-time quantitative PCR and Western blot to detect changes in viral nucleic acid and protein ex pression levels after drug treatment. Additionally, molecular docking and molecular dynamics simulations were utilized to analyze the interaction modes between drugs and key viral targets like 3CLpro and RdRp. The results indicate that certain nucleoside analogs effectively inhibit viral RNA synthesis, while non-nucleoside drugs primarily interfere with viral protein functions. Notably, a novel compound was found to specifically bind to the active site of 3CLpro with high affinity, significantly reducing viral replication capacity. Furthermore, we explored the potential of drugs to influence cytokine storm production in host cells, revealing that specific drug combinations can modulate immune response-related signaling pathways, thereby alleviating inflammatory responses. In conclusion, multiple antiviral drugs exert inhibitory effects on SARS-CoV-2 through different mechanisms; the novel compound offers a new direction for anti-COVID-19 drug development, and combination therapy may improve patient outcomes and reduce complications.
Keywords：Covid-19 Inhibition；Anti-Viral Drugs；3CLpro
目 录
摘 要 I
Abstract II
引 言 1
第一章 新冠病毒的生物学特性 2
1.1 病毒结构与组成 2
1.2 感染机制解析 2
1.3 病毒变异特征 3
第二章 抗病毒药物筛选方法 5
2.1 药物筛选平台 5
2.2 体外实验模型 5
2.3 高通量筛选技术 6
第三章 抗病毒药物作用机制 8
3.1 病毒入侵抑制 8
3.2 病毒复制阻断 8
3.3 免疫调节作用 9
第四章 临床应用与展望 10
4.1 临床试验进展 10
4.2 联合治疗策略 10
4.3 应用前景分析 11
结 论 12
参考文献 13
致 谢 14
