About: Safety and Efficacy of Avaren-Fc Lectibody Targeting HCV High-Mannose Glycans in a Human Liver Chimeric Mouse Model

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About: Safety and Efficacy of Avaren-Fc Lectibody Targeting HCV High-Mannose Glycans in a Human Liver Chimeric Mouse Model Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Safety and Efficacy of Avaren-Fc Lectibody Targeting HCV High-Mannose Glycans in a Human Liver Chimeric Mouse Model
Creator	Matoba, Nobuyuki Dubuisson, Jean Hamorsky, Krystal Vausselin, Thibaut Dent, Matthew Miyata, Yoshinari Morikawa, Yoshio
Source	Elsevier; PMC
abstract	Background Infection with hepatitis C virus (HCV) remains to be a major cause of morbidity and mortality worldwide despite the recent advent of highly effective direct-acting antivirals. The envelope glycoproteins of HCV are heavily glycosylated with a high proportion of high-mannose glycans (HMGs), which serve as a shield against neutralizing antibodies and assist in the interaction with cell-entry receptors. However, there is no approved therapeutic targeting this potentially druggable biomarker. Methods The anti-HCV activity of AvFc was evaluated through the use of in vitro neutralization assays as well as an in vivo challenge in the PXB chimeric human liver mouse model. Drug toxicity was assessed by histopathology, serum ALT, and mouse body weights. Results AvFc was capable of neutralizing cell culture-derived HCV in a genotype-independent manner, with IC50 values in the low nanomolar range. Systemic administration of AvFc in a histidine-based buffer was well tolerated; after 11 doses every other day at 25 mg/kg there were no significant changes in body or liver weights or in blood human albumin or serum ALT activity. Gross necropsy and liver pathology confirmed the lack of toxicity. This regimen successfully prevented genotype 1a HCV infection in all animals, while an AvFc mutant lacking HMG binding activity failed. Conclusion These results suggest that targeting envelope HMGs is a promising therapeutic approach against HCV infection, and AvFc may provide a safe and efficacious means to prevent recurrent infection upon liver transplantation in HCV-related end-stage liver disease patients.
has issue date	2020-08-27(xsd:dateTime)
bibo:doi	10.1016/j.jcmgh.2020.08.009
has license	els-covid
sha1sum (hex)	6234f97573b92244c727258fa624e12d86166431
schema:url	https://doi.org/10.1016/j.jcmgh.2020.08.009
resource representing a document's title	Safety and Efficacy of Avaren-Fc Lectibody Targeting HCV High-Mannose Glycans in a Human Liver Chimeric Mouse Model
has PubMed Central identifier	PMC7451001
schema:publication	Cell Mol Gastroenterol Hepatol
resource representing a document's body	covid:6234f97573b92244c727258fa624e12d86166431#body_text
is schema:about of	named entity 'administration' named entity 'The' named entity 'therapeutic' named entity 'ALT' named entity 'infection' named entity 'safety' named entity 'morbidity' named entity 'https' named entity 'envelope' named entity 'end-stage liver disease' named entity 'HCV' named entity 'M.D.' named entity 'envelope' named entity 'Urokinase' named entity 'mortality' named entity 'strategy' named entity 'Ceramic' named entity 'antivirals' named entity 'composition' named entity 'HCV' named entity 'Conclusion' named entity 'Preprint' named entity 'glycan' named entity 'values' named entity 'biotherapeutic' named entity 'liver' named entity 'performed' named entity 'inventor' named entity 'infection' named entity 'infection' named entity 'paper' named entity 'HCV' named entity 'mouse' named entity 'conducted' named entity 'biomarker' named entity 'This' named entity 'severe' named entity 'Word count' named entity 'entry inhibitor' named entity 'HCV' named entity 'HCV' named entity 'Journal' named entity 'AvFc' named entity 'end-stage liver disease' named entity 'HCV' named entity 'antiviral' named entity 'Data analysis' named entity 'pharmacokinetic' named entity 'Urokinase plasminogen activator' named entity 'AvFc' named entity 'genotype' named entity 'Hepatitis C virus' named entity 'antivirals' named entity 'glycans' named entity 'Infection' named entity 'human albumin' named entity 'Systemic administration' named entity 'infection' named entity 'alanine aminotransferase' named entity 'Drug toxicity' named entity 'HCV' named entity 'cell culture' named entity 'antiviral therapy' named entity 'HCV' named entity 'Chimeric' named entity 'humoral immunity' named entity 'HCV' named entity 'AvFc' named entity 'AvFc' named entity 'mice' named entity 'AvFc' named entity 'toxicity' named entity 'i.p. administration' named entity 'lectin' named entity 'mice' named entity 'toxicity' named entity 'infection'

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