We uncovered small molecules such as camptothecin, importazole, and withaferin A, which can potentially reverse COVID-19 associated gene signatures. L1000 fireworks display (L1000FWD) and L1000 characteristic direction signature search engine (L1000 CDS 2) web tools were used to uncover the small molecules that could potentially reverse the COVID-19 and Neuro-COVID-associated gene signatures. Additionally, single-cell transcriptomics data (GSE163005) of meta clusters of immune cells from the cerebrospinal fluid (CSF), such as T-cells/natural killer cells (NK) (TcMeta), dendritic cells (DCMeta), and monocytes/granulocyte (monoMeta) cell types for comparison, namely, Neuro-COVID versus idiopathic intracranial hypertension (IIH), were analyzed using iPathwayGuide. Here, we used the raw RNA-seq reads (Single-End) in quadruplicates derived using Illumina Next Seq 500 from SARS-CoV-infected primary human bronchial epithelium (NHBE) and mock-treated NHBE cells obtained from the Gene Expression Omnibus (GEO) (GSE147507), and the quality control (QC) was evaluated using the CLC Genomics Workbench 20.0 (Qiagen, United States) before the RNA-seq analysis using BioJupies web tool and iPathwayGuide for gene ontologies (GO), pathways, upstream regulator genes, small molecules, and natural products. The gene expression profiles of COVID-19 infection models can be used to decipher potential therapeutics for COVID-19 and related pathologies, such as Neuro-COVID.
SARS-CoV-2 is the causative agent for coronavirus disease-19 (COVID-19) and belongs to the family Coronaviridae that causes sickness varying from the common cold to more severe illnesses such as severe acute respiratory syndrome, sudden stroke, neurological complications (Neuro-COVID), multiple organ failure, and mortality in some patients. 3Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.2Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.1Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.Peter Natesan Pushparaj 1,2*, Angham Abdulrahman Abdulkareem 1,3 and Muhammad Imran Naseer 1,2*