Direct‐acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow‐spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad‐spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed.

中文翻译：

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靶向宿主抗病毒药物的药物化学策略。

直接作用抗病毒药物 (DAA) 是一类靶向病毒蛋白的药物，已被证明在临床上非常成功地对抗病毒感染。然而，DAAs 存在一些固有的局限性，包括窄谱抗病毒特性和耐药性，因此在治疗病毒感染方面仍有未满足的需求。相比之下，宿主靶向抗病毒药物 (HTA) 靶向宿主因子进行抗病毒治疗。由于各种病毒感染可能广泛需要宿主蛋白，因此 HTA 不仅被感知，而且还表现出广谱抗病毒活性。此外，宿主蛋白不受病毒基因组的遗传控制，因此与 DAA 相比，HTA 具有更高的耐药性遗传屏障。最近几年，随着趋化因子受体 5 型拮抗剂 maraviroc 获批用于人类免疫缺陷病毒治疗，HTA 的开发取得了很大进展，其他病毒感染也正在筹备中。在这篇综述中，我们从药物化学的角度总结了各种宿主蛋白​​作为抗病毒靶点。还讨论了与 HTA 相关的挑战和问题。