Deciphering SARS CoV-2-associated pathways from RNA sequencing data of COVID-19-infected A549 cells and potential therapeutics using in silico methods.

BACKGROUND: Coronavirus (CoV) disease (COVID-19) identified in Wuhan, China, in 2019, is mainly characterized by atypical pneumonia and severe acute respiratory syndrome (SARS) and is caused by SARS CoV-2, which belongs to the Coronaviridae family. Determining the underlying disease mechanisms is central to the identification and development of COVID-19-specific drugs for effective treatment and prevention of human-to-human transmission, disease complications, and deaths. METHODS: Here, next-generation RNA sequencing (RNA Seq) data were obtained using Illumina Next Seq 500 from SARS CoV-infected A549 cells and mock-treated A549 cells from the Gene Expression Omnibus (GEO) (GSE147507), and quality control (QC) was assessed before RNA Seq analysis using CLC Genomics Workbench 20.0. Differentially expressed genes (DEGs) were imported into BioJupies to decipher COVID-19 induced signaling pathways and small molecules derived from chemical synthesis or natural sources to mimic or reverse COVID -19 specific gene signatures. In addition, iPathwayGuide was used to identify COVID-19-specific signaling pathways, as well as drugs and natural products with anti-COVID-19 potential. RESULTS: Here, we identified the potential activation of upstream regulators such as signal transducer and activator of transcription 2 (STAT2), interferon regulatory factor 9 (IRF9), and interferon beta (IFNß), interleukin-1 beta (IL-1ß), and interferon regulatory factor 3 (IRF3). COVID-19 infection activated key infectious disease-specific immune-related signaling pathways such as influenza A, viral protein interaction with cytokine and cytokine receptors, measles, Epstein-Barr virus infection, and IL-17 signaling pathway. Besides, we identified drugs such as prednisolone, methylprednisolone, diclofenac, compound JQ1, and natural products such as Withaferin-A and JinFuKang as candidates for further experimental validation of COVID-19 therapy. CONCLUSIONS: In conclusion, we have used the in silico next-generation knowledge discovery (NGKD) methods to discover COVID-19-associated pathways and specific therapeutics that have the potential to ameliorate the disease pathologies associated with COVID-19.

Disease associated cellular machinery in anaphylaxis - And the de novo paradigm shift.

Anaphylaxis is a sudden immune reaction against an allergen that can potentially lead to Anaphylactic Shock (AS). This immune reaction is characterized by an increase in Immunoglobulin-E (IgE) type of antibodies that bind with FcεRI receptors on mast cells to release inflammatory mediators. Various intracellular signaling molecules downstream of IgE/ FcεRI axis play a potential role in cytokine, chemokine and eicosanoid secretion as well as degranulation of immune cells causing vasodilation, vascular permeability, and reduction of intravascular volume leading to cardiovascular collapse. Here, we discuss the cellular machinery of anaphylaxis and the de novo paradigm shift in the cellular aspects of AS.