Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, 250012 Jinan, Shandong, PR China.
Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Qingdao 266237, PR China.
Drug Resist Updat. 2024 Mar;73:101053. doi: 10.1016/j.drup.2024.101053. Epub 2024 Jan 26.
Viral infections have a major impact in human health. Ongoing viral transmission and escalating selective pressure have the potential to favor the emergence of vaccine- and antiviral drug-resistant viruses. Target-based approaches for the design of antiviral drugs can play a pivotal role in combating drug-resistant challenges. Drug design computational tools facilitate the discovery of novel drugs. This review provides a comprehensive overview of current drug design strategies employed in the field of antiviral drug resistance, illustrated through the description of a series of successful applications. These strategies include technologies that enhance compound-target affinity while minimizing interactions with mutated binding pockets. Furthermore, emerging approaches such as virtual screening, targeted protein/RNA degradation, and resistance analysis during drug design have been harnessed to curtail the emergence of drug resistance. Additionally, host targeting antiviral drugs offer a promising avenue for circumventing viral mutation. The widespread adoption of these refined drug design strategies will effectively address the prevailing challenge posed by antiviral drug resistance.
病毒感染对人类健康有重大影响。持续的病毒传播和不断增加的选择性压力有可能导致疫苗和抗病毒药物耐药病毒的出现。基于靶点的抗病毒药物设计方法可以在应对耐药性挑战方面发挥关键作用。药物设计计算工具有助于发现新的药物。本文通过描述一系列成功的应用,全面概述了当前用于抗病毒药物耐药性领域的药物设计策略。这些策略包括增强化合物与靶标亲和力同时最小化与突变结合口袋相互作用的技术。此外,虚拟筛选、靶向蛋白/RNA 降解和药物设计过程中的耐药性分析等新兴方法已被用于遏制耐药性的出现。此外,针对宿主的抗病毒药物为规避病毒突变提供了一个有前途的途径。这些经过改进的药物设计策略的广泛采用将有效地解决抗病毒药物耐药性带来的普遍挑战。