Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), DPI/NCATS, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Sci Rep. 2021 Mar 24;11(1):6725. doi: 10.1038/s41598-021-86110-8.
The recent global pandemic of the Coronavirus disease 2019 (COVID-19) caused by the new coronavirus SARS-CoV-2 presents an urgent need for the development of new therapeutic candidates. Many efforts have been devoted to screening existing drug libraries with the hope to repurpose approved drugs as potential treatments for COVID-19. However, the antiviral mechanisms of action of the drugs found active in these phenotypic screens remain largely unknown. In an effort to deconvolute the viral targets in pursuit of more effective anti-COVID-19 drug development, we mined our in-house database of approved drug screens against 994 assays and compared their activity profiles with the drug activity profile in a cytopathic effect (CPE) assay of SARS-CoV-2. We found that the autophagy and AP-1 signaling pathway activity profiles are significantly correlated with the anti-SARS-CoV-2 activity profile. In addition, a class of neurology/psychiatry drugs was found to be significantly enriched with anti-SARS-CoV-2 activity. Taken together, these results provide new insights into SARS-CoV-2 infection and potential targets for COVID-19 therapeutics, which can be further validated by in vivo animal studies and human clinical trials.
由新型冠状病毒 SARS-CoV-2 引起的 2019 年冠状病毒病（COVID-19）的全球大流行，迫切需要开发新的治疗候选药物。人们已经投入了大量的努力来筛选现有的药物库，希望将已批准的药物重新用于治疗 COVID-19。然而，在这些表型筛选中发现的有效药物的抗病毒作用机制在很大程度上仍然未知。为了分离病毒靶点，以寻求更有效的抗 COVID-19 药物开发，我们挖掘了我们内部的针对 994 项测定的已批准药物筛选数据库，并将它们的活性谱与 SARS-CoV-2 的细胞病变效应（CPE）测定中的药物活性谱进行了比较。我们发现自噬和 AP-1 信号通路的活性谱与抗 SARS-CoV-2 的活性谱显著相关。此外，一类神经病/精神病学药物被发现具有显著的抗 SARS-CoV-2 活性。总之，这些结果为 SARS-CoV-2 感染提供了新的见解，并为 COVID-19 治疗提供了潜在的靶点，这些靶点可以通过体内动物研究和人类临床试验进一步验证。
