Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, Health Science Campus, Mail Stop #1007, 3000 Arlington Avenue, Toledo, OH, 43614-2598, USA.
Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH, USA.
Sci Rep. 2021 Feb 24;11(1):4495. doi: 10.1038/s41598-021-84044-9.
The COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an "omics" repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.
由新型 SARS-CoV-2 引起的 COVID-19 比其他冠状病毒更具传染性,死亡率比流感更高。鉴定有效的治疗方法是治疗感染 SARS-CoV-2 患者并限制这种新型疾病在全球传播的重要手段。我们部署了一个生物信息学工作流程来鉴定治疗 COVID-19 的候选药物。我们使用“组学”库——集成网络细胞特征库(LINCS),同时探测假定的 COVID-19 药物的转录组特征和公开的 SARS-CoV-2 感染细胞系,以鉴定新的治疗方法。我们确定了一份 20 种候选药物的清单:其中 8 种已在临床试验中用于治疗 COVID-19,其余 12 种具有抗病毒特性,其中 6 种对冠状病毒具有特异性的体外抗病毒功效。所有候选药物均已获得 FDA 批准或正在研究中。我们的候选药物发现与体外产生的 SARS-CoV-2 转录组特征不一致(即相反),并且在 COVID-19 患者样本的转录组特征中也发现了一部分,如 MEK 抑制剂 selumetinib。总的来说,我们的发现为已经作为 COVID-19 治疗药物进行探索的药物提供了额外的支持,并确定了一些有前途的新靶点,值得进一步研究。