Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan.
Department of Chemistry, University of Sahiwal, Sahiwal 57000, Pakistan.
Curr Med Chem. 2021;28(22):4484-4498. doi: 10.2174/0929867327666201027153617.
The 2019 novel coronavirus (2019-nCoV), also known as coronavirus 2 (SARS-CoV-2) acute respiratory syndrome has recently emerged and continued to spread rapidly with high mortality and morbidity rates. Currently, no efficacious therapy is available to relieve coronavirus infections. As new drug design and development takes time, there is a possibility offindingan effective treatment from existing antiviral agents.
The aim of this study is to find out the relationship between thepossible drug targets and themechanism of action of antiviral drugs. This review discusses the efforts indevelopingdrug from known or new molecules.
Viruses usually have two structural integrities, proteins and nucleic acids, both of which can be possible drug targets. Herein, we systemically discuss the structural-functional relationships of the spike, 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro) and RNA-dependent RNA polymerase (RdRp), as these are prominent structural features of thecoronavirus. Certain antiviral drugs such as Remdesivir are RNA-dependent RNA polymerase inhibitorswiththe ability to terminate RNA replication by inhibiting ATP.
It is reported that ATP is involved in synthesis of coronavirus non-structural proteins from 3CLpro and PLpro. Similarly, mechanisms of action of many other antiviral agents havebeen discussed in this review. It will provide new insights into the mechanism of inhibition, and let us develop new therapeutic antiviral approaches against novel SARS-CoV-2 coronavirus.
In conclusion, this review summarizes recent progress in developing protease inhibitors for SARS-CoV-2.
2019 年新型冠状病毒(2019-nCoV),也称为冠状病毒 2(SARS-CoV-2)急性呼吸道疾病最近出现并持续迅速传播,死亡率和发病率高。目前,尚无有效的疗法可缓解冠状病毒感染。由于新药设计和开发需要时间,因此有可能从现有抗病毒药物中找到有效的治疗方法。
本研究旨在探讨可能的药物靶点与抗病毒药物作用机制之间的关系。本综述讨论了从已知或新分子中开发药物的努力。
病毒通常具有两种结构完整性,蛋白质和核酸,两者都可能成为药物靶点。在此,我们系统地讨论了刺突、3-糜蛋白酶样蛋白酶(3CLpro)、木瓜蛋白酶样蛋白酶(PLpro)和 RNA 依赖性 RNA 聚合酶(RdRp)的结构-功能关系,因为这些是冠状病毒的突出结构特征。某些抗病毒药物,如瑞德西韦,是 RNA 依赖性 RNA 聚合酶抑制剂,能够通过抑制 ATP 终止 RNA 复制。
据报道,ATP 参与了 3CLpro 和 PLpro 从冠状病毒非结构蛋白的合成。同样,本综述讨论了许多其他抗病毒药物的作用机制。这将为抑制机制提供新的见解,并使我们能够针对新型 SARS-CoV-2 冠状病毒开发新的治疗性抗病毒方法。
总之,本综述总结了最近在开发针对 SARS-CoV-2 的蛋白酶抑制剂方面的进展。