Virus Details


VHFID1546

Host Factor Information

Gene Name MARK3
HF Protein Name MAP/microtubule affinity-regulating kinase 3
HF Function Essential for viral replication
Uniprot ID P27448
Protein Sequence View Fasta Sequence
NCBI Gene ID 4140
Host Factor (HF) Name in Paper MARK3
Gene synonyms CTAK1 EMK2
Ensemble Gene ID ENSG00000075413
Ensemble Transcript ENST00000216288 [P27448-6];ENST00000303622 [P27448-3];ENST00000416682 [P27448-2];ENST00000429436 [P27448-5];ENST00000440884 [P27448-8];ENST00000553942 [P27448-4]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0000165, GO:0000226, GO:0004674, GO:0005524, GO:0005829, GO:0005886, GO:0030010, GO:0035331, GO:0070062,
MINT ID P27448
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 602678
PANTHER ID PTHR24346;PTHR24346:SF1
PDB ID(s) 2QNJ, 3FE3,
pfam ID PF02149, PF00069, PF00627,
Drug Bank ID N.A.,
ChEMBL ID CHEMBL5600
Organism Homo sapiens (Human)

Pathogen Information

Virus Name Human SARS coronavirus
Virus Short Name SARS-CoV
Order Nidovirales
Virus Family Coronaviridae
Virus Subfamily Coronavirinae
Genus Betacoronavirus
Species Betacoronavirus 1
Host Bats, human
Cell Tropism Epithelial cells of respiratory or enteric tracts, neurological tissues are also frequently infected
Associated Disease Mainly respiratory diseases
Mode of Transmission Respiratory or fecal-oral in humans
VIPR DB link https://www.viprbrc.org/brc/vipr_allSpecies_search.spg?method=SubmitForm&decorator=corona
ICTV DB link https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/222/coronaviridae
Virus Host DB link http://www.genome.jp/virushostdb/view/?virus_lineage=Coronaviridae

Publication Information

Paper Title The SARS-coronavirus-host Interactome: Identification of cyclophilins as Target for Pan Coronavirus Inhibitors
Author's Name Susanne Pfefferle, Julia Schopf, Manfred Kogl, Caroline C. Friedel, Marcel A. Muller, Javier Carbajo-Lozoya, Thorsten Stellberger, Ekatarina von DallArmi, Petra Herzog, Stefan Kallies, Daniela Niemeyer, Vanessa Ditt, Thomas Kuri, Roland Zust, Ksenia Pumpor, Rolf Hilgenfeld, Frank Schwarz, Ralf Zimmer, Imke Steffen, Friedemann Weber, Volker Thiel, Georg Herrler, Heinz-Jurgen Thiel,Christel Schwegmann-Weßels, Stefan Pohlmann, Jurgen Haas, Christian Drosten, and Albrecht von Brunn
Journal Name PLoS PATHOGENS
Pubmed ID 22046132
Abstract Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock.
Used Model HEK293, HEK293lp (low passage), Vero E6, CaCo-2, HRT 18, Huh 7, FCWF- and St-cells
DOI 10.1371/journal.ppat.1002331