dc.contributor.author
Karlas, Alexander
dc.contributor.author
Berre, Stefano
dc.contributor.author
Couderc, Therese
dc.contributor.author
Varjak, Margus
dc.contributor.author
Braun, Peter
dc.contributor.author
Meyer, Michael
dc.contributor.author
Gangneux, Nicolas
dc.contributor.author
Karo-Astover, Liis
dc.contributor.author
Weege, Friderike
dc.contributor.author
Raftery, Martin
dc.contributor.author
Schoenrich, Guenther
dc.contributor.author
Klemm, Uwe
dc.contributor.author
Wurzlbauer, Anne
dc.contributor.author
Bracher, Franz
dc.contributor.author
Merits, Andres
dc.contributor.author
Meyer, Thomas F.
dc.contributor.author
Lecuit, Marc
dc.date.accessioned
2018-06-08T03:55:32Z
dc.date.available
2016-05-30T09:00:21.898Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/16223
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-20407
dc.description.abstract
Chikungunya virus (CHIKV) is a globally spreading alphavirus against which
there is no commercially available vaccine or therapy. Here we use a genome-
wide siRNA screen to identify 156 proviral and 41 antiviral host factors
affecting CHIKV replication. We analyse the cellular pathways in which human
proviral genes are involved and identify druggable targets. Twenty-one small-
molecule inhibitors, some of which are FDA approved, targeting six proviral
factors or pathways, have high antiviral activity in vitro, with low toxicity.
Three identified inhibitors have prophylactic antiviral effects in mouse
models of chikungunya infection. Two of them, the calmodulin inhibitor
pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic
effect in vivo when combined. These results demonstrate the value of loss-of-
function screening and pathway analysis for the rational identification of
small molecules with therapeutic potential and pave the way for the
development of new, host-directed, antiviral agents.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Biological science
dc.subject
Medical research
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie
dc.title
A human genome-wide loss-of-function screen identifies effective chikungunya
antiviral drugs
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Nature Communications. - 7 (2016), Artikel Nr. 11320
dcterms.bibliographicCitation.doi
10.1038/ncomms11320
dcterms.bibliographicCitation.url
http://www.nature.com/ncomms/2016/160512/ncomms11320/full/ncomms11320.html
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000024629
refubium.note.author
Der Artikel wurde in einer Open-Access--Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000006475
dcterms.accessRights.openaire
open access