nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory network
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Khurana et al. ExRNA (2020) 2:16 https://doi.org/10.1186/s41544-020-00057-y
RESEARCH
Open Access
nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks P. Khurana*, A. Gupta, R. Sugadev, Y. K. Sharma, R. Varshney, L. Ganju and B. Kumar
Abstract Background: Given the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARSCoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates have created a new race to curb the disease. While the molecular signature of nSARS-CoV-2 is still under investigation, growing literature shows similarity among nSARS-CoV-2, pulmonary edema, and thromboembolic disorders due to common symptomatic features. A network medicine approach is used to to explore the molecular complexity of the disease and to uncover common molecular trajectories of edema and thrombosis with nSARS-CoV-2. Results and conclusion: A comprehensive nSARS-CoV-2 responsive miRNA: Transcription Factor (TF): gene coregulatory network was built using host-responsive miRNAs and it’s associated tripartite, Feed-Forward Loops (FFLs) regulatory circuits were identified. These regulatory circuits regulate signaling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. A unique miRNA-gene regulatory circuit containing a consortium of four hub FFL motifs is proposed to regulate the virus-endocytosis and antigen-presentation signaling pathways. These regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection, pulmonary diseases and thromboembolic disorders and thus could pave way for repurposing of drugs. Some important miRNAs and genes have also been proposed as potential candidate markers. A detailed molecular snapshot of TGF signaling as the common pathway, that could play an important role in controlling common pathophysiologies among diseases, is also put forth. Keywords: nSARS-CoV-2, miRNA coregulatory networks, Pulmonary edema, Thrombosis, Feed forward loops
Introduction Coronaviruses are retroviruses that are sub-categorized as positive sense single stranded RNA viruses [1]. They belong to Order: Nidovirales; Suborder: Coronavirineae; Family: Coronaviridae; Subfamily: Orthocoronavirinae; Genus: Betacoronavirus; Subgenus: Sarbecovirus; Species: Severe acute respiratory syndrome coronavirus 2. Their genomes size is of ~ 30 kb that includes a 5′cap * Correspondence: [email protected] Defence Institute of Physiology and Allied Sciences, Defence R&D Organization, Lucknow Road, Timarpur, New Delhi, India
structure and a 3′polyA tail [2]. The different coronaviruses can be further classified into four types: α, β, γ, and δ based on specific genomic and protein regions [3]. Novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) belongs to the β subtype of the coronavirus,
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