About: Benzimidazole analogs inhibit respiratory syncytial virus G protein function

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Benzimidazole analogs inhibit respiratory syncytial virus G protein function
Creator	Atkins, Colm Pathak, Ashish Noah, James Evans, Carrie Gilbert, Brian
Source	Elsevier; Medline; PMC
abstract	Abstract Human respiratory syncytial virus (hRSV) is a highly contagious Paramyxovirus that infects most children by age two, generating an estimated 75,000–125,000 hospitalizations in the U.S. annually. hRSV is the most common cause of bronchiolitis and pneumonia among infants and children under 1year of age, with significant mortality among high-risk groups. A regulatory agency-approved vaccine is not available, and existing prophylaxis and therapies are limited to use in high-risk pediatric patients; thus additional therapies are sorely needed. Here, we identify a series of benzimidazole analogs that inhibit hRSV infection in vitro with high potency, using a previously-reported high-throughput screening assay. The lead compound, SRI 29365 (1-[6-(2-furyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]methyl-1H-benzimidazole), has an EC50 of 66μM and a selectivity >50. We identified additional compounds with varying potencies by testing commercially-available chemical analogs. Time-of-addition experiments indicated that SRI 29365 effectively inhibits viral replication only if present during the early stages of viral infection. We isolated a virus with resistance to SRI 29365 and identified mutations in the transmembrane domain of the viral G protein genomic sequence that suggested that the compound inhibits G-protein mediated attachment of hRSV to cells. Additional experiments with multiple cell types indicated that SRI 29365 antiviral activity correlates with the binding of cell surface heparin by full-length G protein. Lastly, SRI 29365 did not reduce hRSV titers or morbidity/mortality in efficacy studies using a cotton rat model. Although SRI 29365 and analogs inhibit hRSV replication in vitro, this work suggests that the G-protein may not be a valid drug target in vivo.
has issue date	2015-09-30(xsd:dateTime)
bibo:doi	10.1016/j.antiviral.2015.06.016
bibo:pmid	26116756
has license	els-covid
sha1sum (hex)	d1a4bd4968756e4b3b1a8083f093029037086cf1
schema:url	https://doi.org/10.1016/j.antiviral.2015.06.016
resource representing a document's title	Benzimidazole analogs inhibit respiratory syncytial virus G protein function
has PubMed Central identifier	PMC7185459
has PubMed identifier	26116756
schema:publication	Antiviral Research
resource representing a document's body	covid:d1a4bd4968756e4b3b1a8083f093029037086cf1#body_text
is schema:about of	named entity 'G PROTEIN' named entity 'SRI' named entity 'efficacy' named entity 'resistance' named entity 'infants' named entity 'The' named entity 'U.S.' named entity 'pediatric' named entity 'studies' named entity 'respiratory syncytial virus' named entity 'analogs' named entity 'RESPIRATORY SYNCYTIAL VIRUS' named entity 'VIRAL REPLICATION' named entity 'PARAMYXOVIRUS' named entity 'POTENCY' named entity 'HIGHLY' named entity 'CHILDREN' named entity 'GROUPS' named entity 'PREVIOUSLY' named entity 'RESISTANCE TO' named entity 'INDICATED' named entity 'BENZIMIDAZOLE' named entity 'IDENTIFIED' named entity 'DID' named entity 'HIGH-RISK' named entity 'G PROTEIN' named entity '125' named entity 'ATTACHMENT' named entity 'PRESENT' named entity 'PROTEIN ' named entity 'NOT AVAILABLE' named entity 'AGE' named entity 'EARLY STAGES' named entity 'WORK' named entity 'LENGTH' named entity 'HUMAN RESPIRATORY SYNCYTIAL VIRUS' named entity 'TESTING' named entity 'MEDIATED' named entity 'SERIES' named entity 'CELL SURFACE' named entity '282' named entity 'BRONCHIOLITIS' named entity 'COMPOUND' named entity '29365' named entity 'IN VITRO' named entity 'ANTIVIRAL ACTIVITY' named entity 'REPORTED' named entity 'MUTATIONS' named entity 'MORBIDITY' named entity 'TRANSMEMBRANE DOMAIN' named entity 'RAT MODEL' named entity 'CELLS' named entity 'COTTON RAT' named entity 'NEEDED' named entity 'HEPARIN' named entity 'MORTALITY' named entity 'THERAPIES' named entity 'HIGH' named entity 'YEAR' named entity 'INFECTION' named entity 'IDENTIFY' named entity 'EXPERIMENTS' named entity 'ASSAY' named entity 'DRUG TARGET' named entity 'PNEUMONIA' named entity 'VIRAL INFECTION' named entity 'USING' named entity 'BINDING' named entity 'VALID' named entity 'PEDIATRIC' named entity 'LEAD COMPOUND' named entity 'SRI' named entity 'IS A' named entity 'U.S.' named entity 'GENERATING' named entity '5B1' named entity 'HERE'

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