{"database":"GNPS","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://massive-ftp.ucsd.edu/v02/MSV000083536/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":{"citationCount":1,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"omics_type":["Metabolomics"],"submitter":["Thomas Metz","Richard Smith","Ralph Baric","Yoshihiro Kawaoka","Katrina Waters"],"instrument_platform":["LTQ Orbitrap Velos"],"species":["Middle East Respiratory Syndrome-related Coronavirus (ncbitaxon:1335626)","Mus Musculus (ncbitaxon:10090)"],"full_dataset_link":["https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=37c0a034f04e45a4832ec07d2b173925"],"submitter_email":["katrina.waters@pnnl.gov","rbaric@email.unc.edu","thomas.metz@pnnl.gov","yoshihiro.kawaoka@wisc.edu","dick.smith@pnnl.gov"],"submitter_affiliation":["University of Wisconsin - Madison","University of North Carolina - Chapel Hill","Pacific Northwest National Laboratory"],"sample_protocol":[""],"repository":["GNPS"],"file_size":["100"],"ptm_modification":["MS:1002864 - No post-translational-modifications are included in the identified peptides of this dataset"],"data_protocol":[""],"pubmed_abstract":["Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology.","In a compound screen on melanoma cells, we identified FX-11 as one of the compounds inhibiting the growth of sensitive and Encorafenib/Binimetinib-resistant 624Mel and Wm3248 melanoma cells. FX-11, reported to be a lactate dehydrogenase inhibitor (LDHi), did not decrease the NAD<sup>+</sup>/NADH ratio, glucose uptake, or lactate secretion of melanoma cells, unlike other LDH inhibitors we used as controls. Instead, FX-11 increased both the oxygen consumption and the extracellular acidification rate of cells in Seahorse assays, behaving similarly to the mitochondrial uncouplers FCCP and BAM15. FX-11 could also be used as an uncoupler in Mito Stress tests. In addition, FX-11 and BAM15 drastically decreased the mitochondrial membrane potential, in contrast to the LDH inhibitors LDH-IN-I and GNE-140. Finally, FX-11 treatment induced an increase in AMPK and acetyl-CoA carboxylase (ACC) phosphorylation and a decrease in phosphorylation of the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), indicative of AMPK activation by decreased ATP/AMP ratio. The observed AMPK activation seems to be involved in FX-11-mediated cell death since knock-down of AMPKα1 reduced cell death. Specific activation of AMPK by MK8722, on the other hand, increased cell death. Taken together, we provide evidence that FX-11 inhibits the growth of melanoma cells, including drug-resistant ones, through an AMPK-dependent mechanism by acting as a mitochondrial uncoupler. Our data do not support that FX-11 acts as an LDH inhibitor."],"pubmed_title":["A compendium of multi-omics data illuminating host responses to lethal human virus infections.","Targeting the energy metabolism of melanoma cells: FX-11 acts as a mitochondrial uncoupler."],"pubmed_authors":["Eisfeld Amie J AJ, Anderson Lindsey N LN, Fan Shufang S, Walters Kevin B KB, Halfmann Peter J PJ, Westhoff Smith Danielle D, Thackray Larissa B LB, Tan Qing Q, Sims Amy C AC, Menachery Vineet D VD, Schäfer Alexandra A, Sheahan Timothy P TP, Cockrell Adam S AS, Stratton Kelly G KG, Webb-Robertson Bobbie-Jo M BM, Kyle Jennifer E JE, Burnum-Johnson Kristin E KE, Kim Young-Mo YM, Nicora Carrie D CD, Peralta Zuleyma Z, N'jai Alhaji U AU, Sahr Foday F, van Bakel Harm H, Diamond Michael S MS, Baric Ralph S RS, Metz Thomas O TO, Smith Richard D RD, Kawaoka Yoshihiro Y, Waters Katrina M KM","Preis Jasmin Renate JR, Rolvering Catherine C, Kirchmeyer Mélanie M, Pereira Catarina Tinoco CT, Faria João J, Behrmann Iris I, Haan Claude C"],"citation_count":["1"],"additional_accession":[]},"is_claimable":false,"name":"GNPS - Mouse lung lipidome response to an icMERS coronavirus MM001","description":"Lipidomics data from infected mouse lungs (n=4) and control (n=3); time points Days 2, 4, and 7","dates":{"publication":"Tue Mar 05 11:25:00 GMT 2019"},"accession":"MSV000083536","cross_references":{"pubmed":["38565538"]}}