Zhao Lei, Li Song, Zhong Wu
National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Beijing Sunho Pharmaceutical Co., Ltd., Beijing, China.
Front Pharmacol. 2022 Feb 25;13:840639. doi: 10.3389/fphar.2022.840639. eCollection 2022.
Since the first reports from December 2019, COVID-19 caused an overwhelming global pandemic that has affected 223 countries, seriously endangering public health and creating an urgent need for effective drugs to treat SARS-CoV-2 infection. Currently, there is a lack of safe, effective, and specific therapeutic drugs for COVID-19, with mainly supportive and symptomatic treatments being administered to patients. The preferred option for responding to an outbreak of acute infectious disease is through drug repurposing, saving valuable time that would otherwise be lost in preclinical and clinical research, hastening clinical introduction, and lowering treatment costs. Alternatively, researchers seek to design and discover novel small-molecule candidate drugs targeting the key proteins in the life cycle of SARS-CoV-2 through an in-depth study of the infection mechanism, thus obtaining a number of candidate compounds with favorable antiviral effects in preclinical and clinical settings. There is an urgent need to further elucidate the efficacy and mechanism of action of potential anti-SARS-CoV-2 small-molecule drugs. Herein, we review the candidate small-molecule anti-SARS-CoV-2 drugs in ongoing clinical trials, with a major focus on their mechanisms of action in an attempt to provide useful insight for further research and development of small-molecule compounds against SARS-CoV-2 infection.
自2019年12月首次报告以来，新型冠状病毒肺炎引发了一场席卷全球的大流行，已影响223个国家，严重危及公众健康，并迫切需要有效的药物来治疗严重急性呼吸综合征冠状病毒2感染。目前，新型冠状病毒肺炎缺乏安全、有效且具有特异性的治疗药物，患者主要接受支持性和对症治疗。应对急性传染病爆发的首选方法是药物再利用，这样可以节省在临床前和临床研究中可能会浪费的宝贵时间，加快临床应用，并降低治疗成本。另外，研究人员试图通过深入研究感染机制来设计和发现针对严重急性呼吸综合征冠状病毒2生命周期中关键蛋白的新型小分子候选药物，从而在临床前和临床环境中获得一些具有良好抗病毒效果的候选化合物。迫切需要进一步阐明潜在的抗严重急性呼吸综合征冠状病毒2小分子药物的疗效和作用机制。在此，我们综述正在进行临床试验的候选抗严重急性呼吸综合征冠状病毒2小分子药物，主要关注其作用机制，以期为进一步研发抗严重急性呼吸综合征冠状病毒2感染的小分子化合物提供有益的见解。
