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Understanding the molecular basis of fibrosis, the lethal complication of COVID-19, is urgent. By the analysis of RNA-sequencing data of SARS-CoV-2-infected cells combined with data mining we identified genes involved in COVID-19 progression. To characterize their implication in the fibrosis development we established a correlation matrix based on the transcriptomic data of patients with idiopathic pulmonary fibrosis. With this method, we have identified a cluster of genes responsible for SARS-CoV-2-fibrosis including its entry receptor ACE2 and epidermal growth factor EGF. Then, we developed Vi-Fi scoring—a novel drug repurposing approach and simultaneously quantified antiviral and antifibrotic activities of the drugs based on their transcriptomic signatures. We revealed the strong dual antifibrotic and antiviral activity of EGFR/ErbB inhibitors. Before the in vitro validation, we have clustered 277 cell lines and revealed distinct COVID-19 transcriptomic signatures of the cells with similar phenotypes that defines their suitability for COVID-19 research. By ERK activity monitoring in living lung cells, we show that the drugs with predicted antifibrotic activity downregulate ERK in the host lung cells. Overall, our study provides novel insights on SARS-CoV-2 dependence on EGFR/ERK signaling and demonstrates the utility of EGFR/ErbB inhibitors for COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Pediatric cancers represent a wide variety of different tumors, though they have unique features that distinguish them from adult cancers. Receptor tyrosine kinases KIT and TrkA functions in AML and NB, respectively, are well-characterized. Though expression of these receptors is found in both tumors, little is known about KIT function in NB and TrkA in AML. By combining gene enrichment analysis with multidimensional scaling we showed that pediatric AMLs with t(8;21) or inv16 and high KIT expression levels stand out from other AML subtypes as they share prominent transcriptomic features exclusively with KIT-overexpressing NBs. We showed that AML cell lines had a predominant expression of an alternative TrkAIII isoform, which reportedly has oncogenic features, while NB cell lines had dominating TrkAI-II isoforms. NB cells, on the other hand, had an abnormal ratio of KIT isoforms as opposed to AML cells. Both SCF and NGF exerted protective action against doxorubicin and cytarabine for t(8;21) AML and NB cells. We identified several gene sets both unique and common for pediatric AML and NB, and this expression is associated with KIT or TrkA levels. NMU, DUSP4, RET, SUSD5, NOS1 , and GABRA5 genes are differentially expressed in NBs with high KIT expression and are associated with poor survival in NB. We identified HOXA10, BAG3 , and MARCKS genes that are connected with TrkA expression and are marker genes of poor outcome in AML. We also report that SLC18A2, PLXNC1 , and MRPL33 gene expression is associated with TrkA or KIT expression levels in both AML and NB, and these genes have a prognostic value for both cancers. Thus, we have provided a comprehensive characterization of TrkA and KIT expression along with the oncogenic signatures of these genes across two pediatric tumors. [ABSTRACT FROM AUTHOR]