Predicted SARS-CoV-2 miRNAs associated with epigenetic viral pathogenesis and the detection of new possible drugs for Covid-19

Objective: The outbreak of COVID-19 caused by SARS-CoV-2 has promptly spread worldwide. This study aimed to predict mature miRNA sequences in the SARS-CoV-2 genome, their effects on protein-protein interactions in the affected cells, gene-drug relationships to detect possible drug candidates. Methods: Viral hairpin structure prediction and classification of the hairpins, mutational examination of precursor miRNA candidate sequences, Minimum Free Energy (MFE) and regional entropy analysis, mature miRNA sequences, target gene prediction, gene ontology enrichment and Protein-Protein Interaction (PPI) analysis, gene-drug interactions were performed. Results: A total of 62 candidate hairpins were detected by VMir analysis. Three hairpin structures classified as true precursor miRNAs by miRBoost. Five different mutations were detected in precursor miRNA sequences in 100 SARS-CoV-2 viral genomes. Mutations slightly elevated MFE values and entropy in precursor miRNAs. Gene ontology terms associated with fibrotic pathways and immune system were found to be enriched in PANTHER, KEGG and Wiki pathway analysis. PPI analysis showed a network between 60 genes. CytoHubba analysis showed SMAD1 as a hub gene in the network. The targets of the predicted miRNAs, FAM214A, PPM1E, NUFIP2 and FAT4 were downregulated in SARS-CoV-2 infected A549 cells. Conclusion: miRNAs in the SARS-CoV-2 virus genome may contribute to the emergence of the Covid-19 clinic by activating pathways associated with the fibrosis in the cells infected by the virus and modulating the innate immune system. The hub protein between these pathways may be the SMAD1, which has an effective role in TGF signal transduction.

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Network Pharmacology Integrated Molecular Docking Reveals the Mechanism of Anisodamine Hydrobromide Injection against Novel Coronavirus Pneumonia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5818107 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Jinsong Su ◽

Zixuan Liu ◽

Chuan Liu ◽

Xuanhao Li ◽

Yi Wang ◽

...

Keyword(s):

Gene Ontology ◽

Molecular Docking ◽

Immune System ◽

Protein Interactions ◽

Viral Infections ◽

Interaction Network ◽

Docking Studies ◽

Network Pharmacology ◽

Immune System Diseases ◽

Topological Parameters

Background. The Coronavirus Disease 2019 (COVID-19) outbreak in Wuhan, China, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anisodamine hydrobromide injection (AHI), the main ingredient of which is anisodamine, is a listed drug for improving microcirculation in China. Anisodamine can improve the condition of patients with COVID-19. Materials and Methods. Protein-protein interactions obtained from the String databases were used to construct the protein interaction network (PIN) of AHI using Cytoscape. The crucial targets of AHI PIN were screened by calculating three topological parameters. Gene ontology and pathway enrichment analyses were performed. The intersection between the AHI component proteins and angiotensin-converting enzyme 2 (ACE2) coexpression proteins was analyzed. We further investigated our predictions of crucial targets by performing molecular docking studies with anisodamine. Results. The PIN of AHI, including 172 nodes and 1454 interactions, was constructed. A total of 54 crucial targets were obtained based on topological feature calculations. The results of Gene Ontology showed that AHI could regulate cell death, cytokine-mediated signaling pathways, and immune system processes. KEGG disease pathways were mainly enriched in viral infections, cancer, and immune system diseases. Between AHI targets and ACE2 coexpression proteins, 26 common proteins were obtained. The results of molecular docking showed that anisodamine bound well to all the crucial targets. Conclusion. The network pharmacological strategy integrated molecular docking to explore the mechanism of action of AHI against COVID-19. It provides protein targets associated with COVID-19 that may be further tested as therapeutic targets of anisodamine.

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Transcriptional Response in the Digestive Gland of the King Scallop (Pecten maximus) after the Injection of Domoic Acid

Toxins ◽

10.3390/toxins13050339 ◽

2021 ◽

Vol 13 (5) ◽

pp. 339

Author(s):

Pablo Ventoso ◽

Antonio J. Pazos ◽

Juan Blanco ◽

M. Luz Pérez-Parallé ◽

Juan C. Triviño ◽

...

Keyword(s):

Signal Transduction ◽

Gene Ontology ◽

Immune System ◽

Digestive Gland ◽

Domoic Acid ◽

Differentially Expressed ◽

Pecten Maximus ◽

System Process ◽

Immune System Process ◽

Response To Stress

Some diatom species of the genus Pseudo-nitzschia produce the toxin domoic acid. The depuration rate of domoic acid in Pecten maximus is very low; for this reason, king scallops generally contain high levels of domoic acid in their tissues. A transcriptomic approach was used to identify the genes differentially expressed in the P. maximus digestive gland after the injection of domoic acid. The differential expression analysis found 535 differentially expressed genes (226 up-regulated and 309 down-regulated). Protein–protein interaction networks obtained with the up-regulated genes were enriched in gene ontology terms, such as vesicle-mediated transport, response to stress, signal transduction, immune system process, RNA metabolic process, and autophagy, while networks obtained with the down-regulated genes were enriched in gene ontology terms, such as response to stress, immune system process, ribosome biogenesis, signal transduction, and mRNA processing. Genes that code for cytochrome P450 enzymes, glutathione S-transferase theta-1, glutamine synthase, pyrroline-5-carboxylate reductase 2, and sodium- and chloride-dependent glycine transporter 1 were among the up-regulated genes. Therefore, a stress response at the level of gene expression, that could be caused by the domoic acid injection, was evidenced by the alteration of several biological, cellular, and molecular processes.

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