Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The SARS-CoV-2 pandemic has made it clear that we have a desperate need for antivirals. We present work that the mammalian SKI complex is a broad-spectrum, host-directed, antiviral drug target. Yeast suppressor screening was utilized to find a functional genetic interaction between proteins from influenza A virus (IAV) and Middle East respiratory syndrome coronavirus (MERS-CoV) with eukaryotic proteins that may be potential host factors involved in replication. This screening identified the SKI complex as a potential host factor for both viruses. In mammalian systems siRNA-mediated knockdown of SKI genes inhibited replication of IAV and MERS-CoV. In silico modeling and database screening identified a binding pocket on the SKI complex and compounds predicted to bind. Experimental assays of those compounds identified three chemical structures that were antiviral against IAV and MERS-CoV along with the filoviruses Ebola and Marburg and two further coronaviruses, SARS-CoV and SARS-CoV-2. The mechanism of antiviral activity is through inhibition of viral RNA production. This work defines the mammalian SKI complex as a broad-spectrum antiviral drug target and identifies lead compounds for further development.
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PMID:The SKI complex is a broad-spectrum, host-directed antiviral drug target for coronaviruses, influenza, and filoviruses. 3318 76

The goal of the present investigation is to identify the differentially expressed genes (DEGs) between SARS-CoV-2 infected and normal control samples to investigate the molecular mechanisms of infection with SARS-CoV-2. The microarray data of the dataset E-MTAB-8871 were retrieved from the ArrayExpress database. Pathway and Gene Ontology (GO) enrichment study, protein-protein interaction (PPI) network, modules, target gene-miRNA regulatory network, and target gene-TF regulatory network have been performed. Subsequently, the key genes were validated using an analysis of the receiver operating characteristic (ROC) curve. In SARS-CoV-2 infection, a total of 324 DEGs (76 up- and 248 down-regulated genes) were identified and enriched in a number of associated SARS-CoV-2 infection pathways and GO terms. Hub and target genes such as TP53, HRAS, MAPK11, RELA, IKZF3, IFNAR2, SKI, TNFRSF13C, JAK1, TRAF6, KLRF2, CD1A were identified from PPI network, target gene-miRNA regulatory network, and target gene-TF regulatory network. Study of the ROC showed that ten genes (CCL5, IFNAR2, JAK2, MX1, STAT1, BID, CD55, CD80, HAL-B, and HLA-DMA) were substantially involved in SARS-CoV-2 patients. The present investigation identified key genes and pathways that deepen our understanding of the molecular mechanisms of SARS-CoV-2 infection, and could be used for SARS-CoV-2 infection as diagnostic and therapeutic biomarkers.
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PMID:Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods. 3325 Oct 83