Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Department of Medicinal Chemistry and Molecular Pharmacolgy, Purdue University, West Lafayette, IN 47907, USA.
ChemMedChem. 2020 Jun 4;15(11):907-932. doi: 10.1002/cmdc.202000223. Epub 2020 May 7.
The COVID-19 pandemic caused by SARS-CoV-2 infection is spreading at an alarming rate and has created an unprecedented health emergency around the globe. There is no effective vaccine or approved drug treatment against COVID-19 and other pathogenic coronaviruses. The development of antiviral agents is an urgent priority. Biochemical events critical to the coronavirus replication cycle provided a number of attractive targets for drug development. These include, spike protein for binding to host cell-surface receptors, proteolytic enzymes that are essential for processing polyproteins into mature viruses, and RNA-dependent RNA polymerase for RNA replication. There has been a lot of ground work for drug discovery and development against these targets. Also, high-throughput screening efforts have led to the identification of diverse lead structures, including natural product-derived molecules. This review highlights past and present drug discovery and medicinal-chemistry approaches against SARS-CoV, MERS-CoV and COVID-19 targets. The review hopes to stimulate further research and will be a useful guide to the development of effective therapies against COVID-19 and other pathogenic coronaviruses.
由 SARS-CoV-2 感染引起的 COVID-19 大流行正在以惊人的速度传播,在全球范围内造成了前所未有的卫生紧急情况。目前尚无针对 COVID-19 和其他致病性冠状病毒的有效疫苗或批准的药物治疗方法。开发抗病毒药物是当务之急。冠状病毒复制周期中的关键生化事件为药物开发提供了许多有吸引力的靶点。这些靶点包括与宿主细胞表面受体结合的刺突蛋白、对多蛋白加工成成熟病毒至关重要的蛋白酶以及用于 RNA 复制的 RNA 依赖性 RNA 聚合酶。针对这些靶点的药物发现和开发已经取得了很多进展。此外,高通量筛选工作已经确定了多种先导结构,包括天然产物衍生的分子。本综述重点介绍了过去和现在针对 SARS-CoV、MERS-CoV 和 COVID-19 靶点的药物发现和药物化学方法。综述希望能激发进一步的研究,并为开发针对 COVID-19 和其他致病性冠状病毒的有效疗法提供有用的指导。