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About:
Toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay
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wasabi.inria.fr
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Type:
Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay
Creator
Canard, Bruno
Decroly, Etienne
Coutard, Bruno
Guillemot, Jean-Claude
Aouadi, Wahiba
Debart, Françoise
Jung, Marie-Louise
Martin, Baptiste
Morice, Christophe
Contreras, Jean
Ecilia Eydoux, C
Jacques Vasseur, Jean
Qu, Gilles
Source
Elsevier; Medline; PMC
abstract
Abstract Two highly pathogenic human coronaviruses associated with severe respiratory syndromes emerged since the beginning of the century. The severe acute respiratory syndrome SARS-coronavirus (CoV) spread first in southern China in 2003 with about 8000 infected cases in few months. Then in 2012, the Middle East respiratory syndrome (MERS-CoV) emerged from the Arabian Peninsula giving a still on-going epidemic associated to a high fatality rate. CoVs are thus considered a major health threat. This is especially true as no vaccine nor specific therapeutic are available against either SARS- or MERS-CoV. Therefore, new drugs need to be identified in order to develop antiviral treatments limiting CoV replication. In this study, we focus on the nsp14 protein, which plays a key role in virus replication as it methylates the RNA cap structure at the N7 position of the guanine. We developed a high-throughput N7-MTase assay based on Homogenous Time Resolved Fluorescence (HTRF®) and screened chemical libraries (2000 compounds) on the SARS-CoV nsp14. 20 compounds inhibiting the SARS-CoV nsp14 were further evaluated by IC50 determination and their specificity was assessed toward flavivirus- and human cap N7-MTases. Our results reveal three classes of compounds: 1) molecules inhibiting several MTases as well as the dengue virus polymerase activity unspecifically, 2) pan MTases inhibitors targeting both viral and cellular MTases, and 3) inhibitors targeting one viral MTase more specifically showing however activity against the human cap N7-MTase. These compounds provide a first basis towards the development of more specific inhibitors of viral methyltransferases.
has issue date
2017-08-31
(
xsd:dateTime
)
bibo:doi
10.1016/j.antiviral.2017.06.021
bibo:pmid
28676301
has license
els-covid
sha1sum (hex)
46546ca01fdd0a53128bbb11664339efb311754c
schema:url
https://doi.org/10.1016/j.antiviral.2017.06.021
resource representing a document's title
Toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay
has PubMed Central identifier
PMC7113892
has PubMed identifier
28676301
schema:publication
Antiviral Research
resource representing a document's body
covid:46546ca01fdd0a53128bbb11664339efb311754c#body_text
is
schema:about
of
named entity 'IDENTIFICATION'
named entity 'reveal'
named entity 'viral'
named entity 'assessed'
named entity 'development'
named entity 'SARS-CoV'
named entity 'fatality rate'
named entity 'emerged'
named entity 'human'
named entity 'targeting'
named entity 'inhibitors'
named entity 'focus'
named entity 'Toward'
named entity 'VIRAL'
named entity 'FLUORESCENCE'
named entity 'GIVING'
named entity 'SPECIFIC'
named entity 'ONGOING'
named entity 'KEY'
named entity 'ARABIAN PENINSULA'
named entity 'THEIR'
named entity 'PROVIDE'
named entity 'TIME'
named entity 'MTASE'
named entity 'BASED'
named entity 'CASES'
named entity 'LIMITING'
named entity 'SOUTHERN'
named entity 'MIDDLE EAST RESPIRATORY SYNDROME '
named entity 'CHINA'
named entity 'ACTIVITY'
named entity 'FLUORESCENCE'
named entity 'MOLECULES'
covid:arg/46546ca01fdd0a53128bbb11664339efb311754c
named entity 'DEVELOPMENT'
named entity 'PLAYS'
named entity 'STUDY'
named entity 'VIRUS REPLICATION'
named entity 'HIGH'
named entity 'IDENTIFIED'
named entity 'EITHER'
named entity 'METHYLTRANSFERASES'
named entity 'REPLICATION'
named entity 'TARGETING'
named entity 'THREAT'
named entity 'VIRAL AND'
named entity 'EVALUATED'
named entity 'HUMAN'
named entity 'TRUE'
named entity 'INHIBITORS'
named entity 'SPECIFICITY'
named entity 'INHIBITING'
named entity 'INFECTED'
named entity 'SARS-COV'
named entity 'HEALTH'
named entity 'SCREENING'
named entity 'CAP'
named entity 'THERAPEUTIC'
named entity 'NEED'
named entity 'CLASSES'
named entity 'CORONAVIRUS'
named entity 'MONTHS'
named entity 'PATHOGENIC'
named entity 'ASSOCIATED'
named entity 'GUANINE'
named entity 'DENGUE VIRUS'
named entity 'RATE'
named entity 'CELLULAR'
named entity 'THESE'
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