COVID-19 caused by the novel SARS-CoV-2 has been declared a pandemic by the WHO is causing havoc across the entire world. As of May end, about 6 million people have been affected, and 367 166 have died from COVID-19. Recent studies suggest that the SARS-CoV-2 genome shares about 80% similarity with the SARS-CoV-1 while their protein RNA dependent RNA polymerase (RdRp) shares 96% sequence similarity. Remdesivir, an RdRp inhibitor, exhibited potent activity against SARS-CoV-2 in vitro. 3-Chymotrypsin like protease (also known as M^pro) and papain-like protease, have emerged as the potential therapeutic targets for drug discovery against coronaviruses owing to their crucial role in viral entry and host-cell invasion. Crystal structures of therapeutically important SARS-CoV-2 target proteins, namely, RdRp, M^pro, endoribonuclease Nsp15/NendoU and receptor binding domain of CoV-2 spike protein has been resolved, which have facilitated the structure-based design and discovery of new inhibitors. Furthermore, studies have indicated that the spike proteins of SARS-CoV-2 use the Angiotensin Converting Enzyme-2 (ACE-2) receptor for its attachment similar to SARS-CoV-1, which is followed by priming of spike protein by Transmembrane protease serine 2 (TMPRSS2) which can be targeted by a proven inhibitor of TMPRSS2, camostat. The current treatment strategy includes repurposing of existing drugs that were found to be effective against other RNA viruses like SARS, MERS, and Ebola. This review presents a critical analysis of druggable targets of SARS CoV-2, new drug discovery, development, and treatment opportunities for COVID-19.

由新型 SARS-CoV-2 引起的 COVID-19 已被世界卫生组织宣布为大流行病，正在全世界范围内造成严重破坏。截至 5 月底，约 600 万人受到影响，367 166 人死于 COVID-19。最近的研究表明，SARS-CoV-2 基因组与 SARS-CoV-1 具有约 80% 的相似性，而它们的蛋白质 RNA 依赖性 RNA 聚合酶 (RdRp) 具有 96% 的序列相似性。Remdesivir 是一种 RdRp 抑制剂，在体外表现出针对 SARS-CoV-2 的有效活性。3-胰凝乳蛋白酶样蛋白酶（也称为 M ^pro）和木瓜蛋白酶样蛋白酶由于在病毒进入和宿主细胞侵袭中发挥着至关重要的作用，已成为冠状病毒药物研发的潜在治疗靶点。治疗上重要的 SARS-CoV-2 靶蛋白，即 RdRp、M ^pro、核糖核酸内切酶 Nsp15/NendoU 和 CoV-2 刺突蛋白的受体结合域的晶体结构已得到解析，这有助于基于结构的设计和新发现抑制剂。此外，研究表明，SARS-CoV-2 的刺突蛋白与 SARS-CoV-1 类似，使用血管紧张素转换酶 2 (ACE-2) 受体进行附着，随后通过跨膜蛋白酶引发刺突蛋白丝氨酸 2 (TMPRSS2)，经过验证的 TMPRSS2 抑制剂卡莫司他 (camostat) 可以靶向该丝氨酸 2 (TMPRSS2)。目前的治疗策略包括重新利用现有药物，这些药物被发现对其他 RNA 病毒（如 SARS、MERS 和埃博拉）有效。这篇综述对 SARS CoV-2 的药物靶点、新药发现、开发和 COVID-19 的治疗机会进行了批判性分析。