PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, Bonn, Germany.
Department of Chemistry, PSG Institute of Technology and Applied Research, Coimbatore, Tamil Nadu, India.
Med Res Rev. 2021 Jan;41(1):72-135. doi: 10.1002/med.21724. Epub 2020 Aug 27.
Coronaviruses (CoVs) infect both humans and animals. In humans, CoVs can cause respiratory, kidney, heart, brain, and intestinal infections that can range from mild to lethal. Since the start of the 21st century, three β-coronaviruses have crossed the species barrier to infect humans: severe-acute respiratory syndrome (SARS)-CoV-1, Middle East respiratory syndrome (MERS)-CoV, and SARS-CoV-2 (2019-nCoV). These viruses are dangerous and can easily be transmitted from human to human. Therefore, the development of anticoronaviral therapies is urgently needed. However, to date, no approved vaccines or drugs against CoV infections are available. In this review, we focus on the medicinal chemistry efforts toward the development of antiviral agents against SARS-CoV-1, MERS-CoV, SARS-CoV-2, targeting biochemical events important for viral replication and its life cycle. These targets include the spike glycoprotein and its host-receptors for viral entry, proteases that are essential for cleaving polyproteins to produce functional proteins, and RNA-dependent RNA polymerase for viral RNA replication.
冠状病毒（CoVs）既可感染人类也可感染动物。在人类中，CoVs 可引起从轻度到致命的呼吸道、肾脏、心脏、大脑和肠道感染。自 21 世纪初以来，三种β冠状病毒已跨越物种屏障感染人类：严重急性呼吸综合征（SARS）-CoV-1、中东呼吸综合征（MERS）-CoV 和 SARS-CoV-2（2019-nCoV）。这些病毒很危险，很容易在人与人之间传播。因此，急需开发抗冠状病毒疗法。然而，迄今为止，尚无针对 CoV 感染的批准疫苗或药物。在这篇综述中，我们重点介绍了针对 SARS-CoV-1、MERS-CoV 和 SARS-CoV-2 的抗病毒药物开发的药物化学努力，这些药物针对病毒复制及其生命周期中重要的生化事件。这些靶点包括刺突糖蛋白及其宿主受体，用于病毒进入，蛋白酶对于切割多蛋白以产生功能性蛋白是必不可少的，以及 RNA 依赖性 RNA 聚合酶用于病毒 RNA 复制。
