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.

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克服抗病毒药物耐药性的靶向药物设计策略：机遇与挑战

病毒感染对人类健康具有重大影响。持续的病毒传播和不断升级的选择压力有可能有利于疫苗和抗病毒药物耐药病毒的出现。基于目标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新药的发现。本综述全面概述了抗病毒耐药领域当前采用的药物设计策略，并通过一系列成功应用的描述进行了说明。这些策略包括增强化合物-靶标亲和力，同时最大限度地减少与突变结合袋的相互作用的技术。此外，虚拟筛选、靶向蛋白质/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来减少耐药性的出现。此外，针对宿主的抗病毒药物为规避病毒突变提供了一条有希望的途径。这些精细药物设计策略的广泛采用将有效解决抗病毒耐药性带来的普遍挑战。