New Strategies for Responding to SARS-CoV-2: The Present and Future of Dual-Target Drugs,Journal of Medicinal Chemistry

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New Strategies for Responding to SARS-CoV-2: The Present and Future of Dual-Target Drugs
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-07-05 , DOI: 10.1021/acs.jmedchem.4c00384
Wenyi Zhang ₁ , Lecheng Xiao ₁ , Dianyang Li ₂ , Yuxuan Hu ₁ , Wenying Yu ₁

Affiliation

The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths, posing a serious threat to public health and safety. Rapid mutations of SARS-CoV-2 and complex interactions among multiple targets during infection pose a risk of expiry for small molecule inhibitors. This suggests that the traditional concept of “one bug, one drug” could be ineffective in dealing with the coronavirus. The dual-target drug strategy is expected to be the key to ending coronavirus infections. However, the lack of design method and improper combination of dual-targets poses obstacle to the discovery of new dual-target drugs. In this Perspective, we summarized the profiles concerning drug design methods, structure–activity relationships, and pharmacological parameters of dual-target drugs for the treatment of COVID-19. Importantly, we underscored how target combination and rational drug design illuminate the development of dual-target drugs for SARS-CoV-2.

中文翻译：

应对 SARS-CoV-2 的新策略：双靶点药物的现状与未来

由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）大流行已导致数百万人死亡，对公众健康和安全构成严重威胁。 SARS-CoV-2 的快速突变以及感染过程中多个靶点之间复杂的相互作用给小分子抑制剂带来了失效的风险。这表明“一种细菌、一种药物”的传统概念在应对冠状病毒方面可能无效。双靶点药物策略有望成为结束冠状病毒感染的关键。然而，设计方法的缺乏和双靶点组合的不当给新双靶点药物的发现带来了障碍。在这篇文章中，我们总结了治疗COVID-19的双靶点药物的药物设计方法、构效关系和药理参数等方面的概况。重要的是，我们强调了靶点组合和合理的药物设计如何阐明 SARS-CoV-2 双靶点药物的开发。

更新日期：2024-07-05

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