School of Life Sciences, Jilin University, Changchun, 130012, PR China.
Faculty of Pharmacy, Shaanxi University of Science & Technology, Xi'an, 710021, PR China.
Biomed Pharmacother. 2021 May;137:111313. doi: 10.1016/j.biopha.2021.111313. Epub 2021 Feb 3.
The SARS-CoV-2 outbreak and pandemic that began near the end of 2019 has posed a challenge to global health. At present, many candidate small-molecule therapeutics have been developed that can inhibit both the infection and replication of SARS-CoV-2 and even potentially relieve cytokine storms and other related complications. Meanwhile, host-targeted drugs that inhibit cellular transmembrane serine protease (TMPRSS2) can prevent SARS-CoV-2 from entering cells, and its combination with chloroquine and dihydroorotate dehydrogenase (DHODH) inhibitors can limit the spread of SARS-CoV-2 and reduce the morbidity and mortality of patients with COVID-19. The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin. This review also covers inhibitors of 3C-like protease (3CL), papain-like protease (PL) and other potentially innovative active ingredient molecules, describing their potential targets, activities, clinical status and side effects.
2019 年末开始的新型冠状病毒（SARS-CoV-2）爆发和大流行对全球健康构成了挑战。目前，已经开发出许多候选小分子治疗药物，它们可以抑制 SARS-CoV-2 的感染和复制，甚至可能缓解细胞因子风暴和其他相关并发症。同时，靶向宿主的细胞跨膜丝氨酸蛋白酶（TMPRSS2）抑制剂可以阻止 SARS-CoV-2 进入细胞，与氯喹和二氢乳清酸脱氢酶（DHODH）抑制剂联合使用可以限制 SARS-CoV-2 的传播并降低 COVID-19 患者的发病率和死亡率。本文基于药物化学研究的见解，概述了这些小分子治疗药物，重点介绍了 RNA 依赖性 RNA 聚合酶（RdRp）抑制剂，如核苷类似物瑞德西韦、法匹拉韦和利巴韦林。本文还介绍了 3C 样蛋白酶（3CL）、木瓜蛋白酶样蛋白酶（PL）和其他潜在创新活性成分分子的抑制剂，描述了它们的潜在靶点、活性、临床状况和副作用。
