Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Via F.Cervi 93, 20090 Segrate-Milan, Milan, Italy.
Department of Physics "Giuseppe Occhialini", University of Milan-Bicocca Piazza dell'Ateneo Nuovo, 1 - 20126, Milan, Italy.
Viruses. 2020 Apr 6;12(4):404. doi: 10.3390/v12040404.
Previous studies reported that Angiotensin converting enzyme 2 (ACE2) is the main cell receptor of SARS-CoV and SARS-CoV-2. It plays a key role in the access of the virus into the cell to produce the final infection. In the present study we investigated in silico the basic mechanism of in the lung and provided evidences for new potentially effective drugs for Covid-19. Specifically, we used the gene expression profiles from public datasets including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, Gene Ontology and pathway enrichment analysis to investigate the main functions of -correlated genes. We constructed a protein-protein interaction network containing the genes co-expressed with . Finally, we focused on the genes in the network that are already associated with known drugs and evaluated their role for a potential treatment of Covid-19. Our results demonstrate that the genes correlated with are mainly enriched in the sterol biosynthetic process, Aryldialkylphosphatase activity, adenosylhomocysteinase activity, trialkylsulfonium hydrolase activity, acetate-CoA and CoA ligase activity. We identified a network of 193 genes, 222 interactions and 36 potential drugs that could have a crucial role. Among possible interesting drugs for Covid-19 treatment, we found Nimesulide, Fluticasone Propionate, Thiabendazole, Photofrin, Didanosine and Flutamide.
先前的研究报告指出，血管紧张素转换酶 2（ACE2）是 SARS-CoV 和 SARS-CoV-2 的主要细胞受体。它在病毒进入细胞产生最终感染中起着关键作用。在本研究中，我们通过计算机模拟研究了肺中的基本机制，并为新冠病毒提供了新的潜在有效药物的证据。具体来说，我们使用了来自公共数据集的基因表达谱，包括癌症基因组图谱、基因表达综合数据库和基因-组织表达数据库、基因本体论和途径富集分析，以研究与 -相关基因的主要功能。我们构建了一个包含与共表达的基因的蛋白质-蛋白质相互作用网络。最后，我们专注于网络中已经与已知药物相关的基因，并评估它们在新冠病毒治疗中的潜在作用。我们的研究结果表明，与相关的基因主要富集在固醇生物合成过程、芳基二烷基磷酸酶活性、腺苷同型半胱氨酸酶活性、三烷基磺基氢酶活性、乙酸-CoA 和 CoA 连接酶活性中。我们确定了一个由 193 个基因、222 个相互作用和 36 种潜在药物组成的网络，这些药物可能具有关键作用。在治疗新冠病毒的可能的有趣药物中，我们发现了尼美舒利、丙酸氟替卡松、噻苯达唑、Photofrin、地昔洛韦和氟他胺。
