Small molecules in the treatment of COVID-19.
Small molecules in the treatment of COVID-19.
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DOI：
10.1038/s41392-022-01249-8
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发表时间：
2022-12-05
影响因子：
39.3
通讯作者：
Men, Ke
中科院分区：
文献类型：
--
作者：
Lei, Sibei;Chen, Xiaohua;Wu, Jieping;Duan, Xingmei;Men, Ke
COVID-19的爆发已成为一场全球性危机，并对社会及经济带来严重干扰。到目前为止，对COVID-19的有效治疗方法的需求很高。沿着我们对SARS-CoV-2的结构、功能和致病过程的理解不断加深，许多具有潜在抗COVID-19作用的小分子被开发出来。到目前为止，已经探索了几种抗病毒策略。除了直接抑制病毒蛋白（如RdRp和Mpro）外，干扰宿主酶（包括ACE 2和蛋白酶）以及阻断以JAK/STAT、BTK、NF-κB和NLRP 3途径为代表的相关免疫调节途径在药物开发中被认为是可行的。治疗COVID-19的小分子药物的开发已经通过几种策略实现，包括计算机辅助先导化合物设计和筛选、天然产物发现、药物再利用和联合治疗。以瑞德西韦和帕昔洛韦为代表的几种小分子药物已被许多国家批准或批准紧急使用。许多候选人已经进入临床试验阶段。然而，由于SARS-CoV-2的流行病学特征和变异性问题，有必要继续探索新的抗COVID-19策略。这篇综述讨论了目前在开发用于COVID-19治疗的小分子方面的发现。此外，他们的详细的作用机制，化学结构，和临床前和临床疗效进行了讨论。
The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.
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