Computational gene expression profiling in the exploration of biomarkers, non-coding functional RNAs and drug perturbagens for COVID-19

Abstract

The coronavirus disease, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health crisis that is being endured with an increased alarm of transmission each day. Though the pandemic has activated innumerable research attention to decipher an antidote, fundamental understanding of the molecular mechanisms is necessary to halt the disease progression. The study focused on comparison of the COVID-19 infected lung tissue gene expression datasets-GSE155241 and GSE150316 with the GEO2R-limma package. The significant up-and downregulated genes were annotated. Further evaluation of the enriched pathways, transcription factors, kinases, noncoding RNAs and drug perturbations revealed the significant molecular mechanisms of the host response. The results revealed a surge in mitochondrial respiration, cytokines, neurodegenerative mechanisms and deprived oxygen, iron, copper, and glucose transport. Hijack of ubiquitination by SARS-CoV-2, hox gene differentiation, histone modification, and miRNA biogenesis were the notable molecular mechanisms inferred. Long non-coding RNAs such as C058791.1, TTTY15 and TPTEP1 were predicted to be efficient in regulating the disease mechanisms. Drugs-F-1566-0341, Digoxin, Proscillaridin and Linifanib that reverse the gene expression signatures were predicted from drug perturbations analysis. The binding efficiency and interaction of proscillaridin and digoxin as obtained from the molecular docking studies confirmed their therapeutic potential. Two overlapping upregulated genes MDH1, SGCE and one downregulated gene PFKFB3 were appraised as potential biomarkers candidates. The upregulation of PGM5, ISLR and ANK2 as measured from their expressions in normal lungs affirmed their possible prognostic biomarker competence. The study explored significant insights for better diagnosis, and therapeutic options for COVID-19.

Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity

“…reported in other SARS-CoV-2 related papers (Aishwarya et al, 2020;Vastrad et al, 2020). Ankryin B, which aligns to SP597-606, has been reported to be transcribed in lungs of COVID-19 patients, where it is not usually expressed (Aishwarya et al, 2020), and ZNF354C, aligning to NP361-390, is a transcription factor which interacts with genes that are differentially expressed in SARS-CoV-2 infected patients (Vastrad et al, 2020).…”

Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts

“…The authors revealed that proscillaridin A could effectively inhibit the replication of SARS-CoV-2 3CL pro in Vero cells at an IC 50 of 2.04 μM ( Liu et al, 2020a ). Furthermore, proscillaridin A exhibited a low binding energy (−80.06 Kcal/mol) and well interactions (six interactions) with SARS-CoV-2 M pro ; in addition, this study provided additional evidence relating to the potential molecular mechanisms of action ( Aishwarya et al, 2020 ).…”

Molecular Mechanisms of Cardiac Injury Associated With Myocardial SARS-CoV-2 Infection

“…Among these 10 drugs, the cytotoxic drugs chromium (III) chloride and irinotecan hydrochloride should not be considered as candidates. Antimycin A ( 52 ), proscillaridin ( 53 , 54 ), troglitazone ( 55 , 56 ), thapsigargin ( 57 , 58 ), genistein ( 59 , 60 ), and testosterone ( 61 ) were considered as potential drugs for COVID-19 in previous studies. Acetovanillone and hyperforin have not been studied for the treatment of COVID-19.…”