About: Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus
Creator	Thiel, Volker Dijkman, Ronald Drosten, Christian Forlenza, Maria Hannoun, Charles Kann, Nina Kindler, Eveline Kint, Joeri Lundin, Anna Muth, Doreen Trybala, Edward Bergströ, Tomas Jó Nsdó Ttir, Hulda Mü Ller, Marcel
Source	Medline; PMC
abstract	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.
has issue date	2014-05-29(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1004166
bibo:pmid	24874215
has license	cc-by
sha1sum (hex)	17dbd5741595c1e5b7508063b31147be9263e7f0
schema:url	https://doi.org/10.1371/journal.ppat.1004166
resource representing a document's title	Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus
has PubMed Central identifier	PMC4038610
has PubMed identifier	24874215
schema:publication	PLoS Pathog
resource representing a document's body	covid:17dbd5741595c1e5b7508063b31147be9263e7f0#body_text
is schema:about of	named entity 'resistant' named entity 'induced' named entity 'coronavirus' named entity 'Viral' named entity 'PORT' covid:arg/17dbd5741595c1e5b7508063b31147be9263e7f0 named entity 'TARGETING' named entity 'ENTRY' named entity 'ANTIVIRAL DRUGS' named entity 'INFECTIONS' named entity 'VESICLES' named entity 'VIRUS' named entity 'RNA SYNTHESIS' named entity 'HUMAN CORONAVIRUS' named entity 'INDUCED' named entity 'MEMBRANES' named entity 'CORONAVIRUS INFECTION' named entity 'ANTIVIRAL' named entity 'PARADIGM' named entity 'COMBAT' named entity 'VIRUS ENTRY' named entity 'HUMAN VIRUS' named entity 'AVAILABLE' named entity 'VULNERABLE' named entity 'COMPLETE INHIBITION' named entity 'TARGETS' named entity 'REDUCED NUMBER' named entity 'ACTIVITY' named entity 'VIRAL RNA' named entity 'CORONAVIRUSES' named entity 'MEMBRANE' named entity 'INHIBITION' named entity 'DOUBLE' named entity 'RNA VIRUSES' named entity 'BOUND' named entity 'POSITIVE' named entity 'ANIMAL' named entity 'VIRAL REPLICATION COMPLEX' named entity 'INFECTIVITY' named entity 'INCLUDING' named entity 'INHIBITION' named entity 'BOUND' named entity 'MIDDLE EAST RESPIRATORY SYNDROME ' named entity 'DIVERSE' named entity 'BROAD' named entity 'INTERVENTION' named entity 'HUMAN' named entity 'DESIGNATED' named entity 'NEAR' named entity 'STUDY' named entity 'NON-' named entity 'MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS' named entity 'COMPONENT' named entity 'HERE' named entity 'RESISTANT' named entity 'VIRUSES' named entity 'PRIMARY' named entity 'MEMBRANE' named entity 'IMPAIRED' named entity 'DIVERSE' named entity 'TO SERVE AS' named entity 'SPECIFIC' named entity 'DISPLAYED' named entity 'K22' named entity 'CONTAINED' named entity 'NUMBER OF' named entity 'EFFICIENT' named entity 'CELLULAR'

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