The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has arisen as a global pandemic affecting the respiratory system showing acute respiratory distress syndrome (ARDS). However, there is no targeted therapeutic agent yet and due to the growing cases of infections and the rising death tolls, discovery of the possible drug is the need of the hour. In general, the study for discovering therapeutic agent for SARS-CoV-2 is largely focused on large-scale screening with fragment-based drug discovery (FBDD). With the recent advancement in cryo-electron microscopy (Cryo-EM), it has become one of the widely used tools in structural biology. It is effective in investigating the structure of numerous proteins in high-resolution and also had an intense influence on drug discovery, determining the binding reaction and regulation of known drugs as well as leading the design and development of new drug candidates. Here, we review the application of cryo-EM in a structure-based drug design (SBDD) and in silico screening of the recently acquired FBDD in SARS-CoV-2. Such insights will help deliver better understanding in the procurement of the effective remedial solution for this pandemic.

中文翻译：

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冷冻电镜作为药物发现的强大工具：最近对 SARS-CoV-2 的结构研究

新型冠状病毒，严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 已成为影响呼吸系统的全球流行病，表现为急性呼吸窘迫综合征 (ARDS)。然而，目前还没有针对性的治疗药物，并且由于感染病例不断增加和死亡人数不断上升，迫切需要发现可能的药物。一般来说，发现 SARS-CoV-2 治疗剂的研究主要集中在基于片段的药物发现 (FBDD) 的大规模筛选。随着冷冻电子显微镜（Cryo-EM）的最新进展，它已成为结构生物学中广泛使用的工具之一。它可以有效地以高分辨率研究多种蛋白质的结构，并且对药物发现、确定已知药物的结合反应和调节以及引导新候选药物的设计和开发产生巨大影响。在这里，我们回顾了冷冻电镜在基于结构的药物设计 (SBDD) 中的应用以及最近获得的 SARS-CoV-2 FBDD 的计算机筛选。这些见解将有助于更好地了解针对这一流行病采购有效的补救解决方案。