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Sökning: WFRF:(Trybala Edward 1955) > (2010-2014) > Targeting Membrane-...

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FältnamnIndikatorerMetadata
00006008naa a2200709 4500
001oai:gup.ub.gu.se/200709
003SwePub
008240910s2014 | |||||||||||000 ||eng|
009oai:research.chalmers.se:ac7c79c8-cf9d-4c84-9e6b-feab11546469
0247 a https://gup.ub.gu.se/publication/2007092 URI
0247 a https://doi.org/10.1371/journal.ppat.10041662 DOI
0247 a https://research.chalmers.se/publication/2007092 URI
040 a (SwePub)gud (SwePub)cth
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Lundin, Annau Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg4 aut0 (Swepub:gu)xluany
2451 0a Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus
264 c 2014-05-29
264 1b Public Library of Science (PLoS),c 2014
338 a electronic2 rdacarrier
520 a Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.
650 7a NATURVETENSKAPx Biologix Mikrobiologi0 (SwePub)106062 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Microbiology0 (SwePub)106062 hsv//eng
653 a MOUSE HEPATITIS-VIRUS
653 a DOUBLE-STRANDED-RNA
653 a SARS CORONAVIRUS
653 a REPLICATION COMPLEX
653 a MAIN PROTEINASE
653 a FUNCTIONAL RECEPTOR
653 a 3C-LIKE
653 a PROTEINASE
653 a VACCINIA VIRUS
653 a CELL-CULTURES
653 a IN-VITRO
653 a Microbiology
653 a Parasitology
653 a Virology
653 a SARS CORONAVIRUS
7001 a Dijkman, R.u Federal Department of Home Affairs4 aut
7001 a Bergström, Tomas,d 1950u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg4 aut0 (Swepub:gu)xberto
7001 a Kann, Nina,d 1964u Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)kann
7001 a Adamiak, Beatau Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg4 aut0 (Swepub:gu)xadamb
7001 a Hannoun, Charles,d 1967u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg4 aut0 (Swepub:gu)xhchar
7001 a Kindler, E.u Federal Department of Home Affairs4 aut
7001 a Jonsdottir, H. R.u Federal Department of Home Affairs4 aut
7001 a Muth, D.u Universität Bonn,University of Bonn4 aut
7001 a Kint, J.u Wageningen University and Research4 aut
7001 a Forlenza, M.u Wageningen University and Research4 aut
7001 a Muller, M. A.u Universität Bonn,University of Bonn4 aut
7001 a Drosten, C.u Universität Bonn,University of Bonn4 aut
7001 a Thiel, V.u Universität Bern,University of Bern,Federal Department of Home Affairs4 aut
7001 a Trybala, Edward,d 1955u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg4 aut0 (Swepub:gu)xtryed
7102 a Göteborgs universitetb Institutionen för biomedicin, avdelningen för infektionssjukdomar4 org
7730 t Plos Pathogensd : Public Library of Science (PLoS)g 10:5q 10:5x 1553-7366x 1553-7374
8564 u https://gup.ub.gu.se/publication/200709x primaryx freey FULLTEXT
8564 u https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004166&type=printable
8564 u http://publications.lib.chalmers.se/records/fulltext/200709/local_200709.pdfx primaryx freey FULLTEXT
8564 8u https://gup.ub.gu.se/publication/200709
8564 8u https://doi.org/10.1371/journal.ppat.1004166
8564 8u https://research.chalmers.se/publication/200709

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