Sakamuru Srilatha, Huang Ruili, Xia Menghang
Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, MD, United States.
Front Pharmacol. 2022 Jul 14;13:935399. doi: 10.3389/fphar.2022.935399. eCollection 2022.
Currently, various potential therapeutic agents for coronavirus disease-2019 (COVID-19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are being investigated worldwide mainly through the drug repurposing approach. Several anti-viral, anti-bacterial, anti-malarial, and anti-inflammatory drugs were employed in randomized trials and observational studies for developing new therapeutics for COVID-19. Although an increasing number of repurposed drugs have shown anti-SARS-CoV-2 activities , so far only remdesivir has been approved by the US FDA to treat COVID-19, and several other drugs approved for Emergency Use Authorization, including sotrovimab, tocilizumab, baricitinib, paxlovid, molnupiravir, and other potential strategies to develop safe and effective therapeutics for SARS-CoV-2 infection are still underway. Many drugs employed as anti-viral may exert unwanted side effects (i.e., toxicity) via unknown mechanisms. To quickly assess these drugs for their potential toxicological effects and mechanisms, we used the Tox21 assay datasets generated from screening ∼10,000 compounds consisting of approved drugs and environmental chemicals against multiple cellular targets and pathways. Here we summarize the toxicological profiles of small molecule drugs that are currently under clinical trials for the treatment of COVID-19 based on their activities against various targets and cellular signaling pathways.
目前，针对由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的全球大流行疾病2019冠状病毒病（COVID-19），各种潜在治疗药物正在全球范围内主要通过药物重新利用的方法进行研究。几种抗病毒、抗菌、抗疟疾和抗炎药物被用于随机试验和观察性研究，以开发针对COVID-19的新疗法。尽管越来越多重新利用的药物已显示出抗SARS-CoV-2活性，但到目前为止，只有瑞德西韦已被美国食品药品监督管理局（FDA）批准用于治疗COVID-19，其他几种被批准用于紧急使用授权的药物，包括索托维单抗、托珠单抗、巴瑞替尼、帕罗韦德、莫努匹拉韦，以及开发针对SARS-CoV-2感染的安全有效疗法的其他潜在策略仍在进行中。许多用作抗病毒的药物可能通过未知机制产生不良副作用（即毒性）。为了快速评估这些药物的潜在毒理学效应和机制，我们使用了Tox21检测数据集，该数据集来自对约10000种由批准药物和环境化学品组成的化合物针对多个细胞靶点和通路的筛选。在此，我们根据小分子药物对各种靶点和细胞信号通路的活性，总结了目前正在进行治疗COVID-19临床试验的小分子药物的毒理学概况。
