Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice.
Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assemb...
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2011
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oai:doaj.org-article:ce3067c018d44286925e45fb1cf480f72021-11-18T07:33:04ZAntiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice.1932-620310.1371/journal.pone.0025096https://doaj.org/article/ce3067c018d44286925e45fb1cf480f72011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22162746/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assembly. The aim of this study was to determine the antiviral effect of Bay 41-4109 in a mouse model with humanized liver and the spread of active HBV. Antiviral assays of Bay 41-4109 on HepG2.2.15 cells constitutively expressing HBV, displayed an IC(50) of about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with human hepatocytes and infected with HBV. Ten days post-infection, the mice were treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV load was evaluated by quantitative PCR. At the end of treatment, decreased HBV viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV viremia of about 0.5 log(10) copies/ml was measured in the control group. Five days after the end of treatment, a rebound of HBV viremia occurred in the treated group. Furthermore, 15 days after treatment discontinuation, a similar expression of the viral capsid was evidenced in liver biopsies. Our findings demonstrate that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb-uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a new strategy for the treatment of patients in escape from standard antiviral therapy.Nicolas BrezillonMarie-Noëlle BrunelleHélène MassinetEric GiangCéline LamantLucie DaSilvaSophie BerissiJacques BelghitiLaurent HannounGherard PuerstingerEva WimmerJohan NeytsOlivier HantzPatrick SoussanSerban MorosanDina KremsdorfPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e25096 (2011) |
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Medicine R Science Q Nicolas Brezillon Marie-Noëlle Brunelle Hélène Massinet Eric Giang Céline Lamant Lucie DaSilva Sophie Berissi Jacques Belghiti Laurent Hannoun Gherard Puerstinger Eva Wimmer Johan Neyts Olivier Hantz Patrick Soussan Serban Morosan Dina Kremsdorf Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice. |
| description |
Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assembly. The aim of this study was to determine the antiviral effect of Bay 41-4109 in a mouse model with humanized liver and the spread of active HBV. Antiviral assays of Bay 41-4109 on HepG2.2.15 cells constitutively expressing HBV, displayed an IC(50) of about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with human hepatocytes and infected with HBV. Ten days post-infection, the mice were treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV load was evaluated by quantitative PCR. At the end of treatment, decreased HBV viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV viremia of about 0.5 log(10) copies/ml was measured in the control group. Five days after the end of treatment, a rebound of HBV viremia occurred in the treated group. Furthermore, 15 days after treatment discontinuation, a similar expression of the viral capsid was evidenced in liver biopsies. Our findings demonstrate that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb-uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a new strategy for the treatment of patients in escape from standard antiviral therapy. |
| format |
article |
| author |
Nicolas Brezillon Marie-Noëlle Brunelle Hélène Massinet Eric Giang Céline Lamant Lucie DaSilva Sophie Berissi Jacques Belghiti Laurent Hannoun Gherard Puerstinger Eva Wimmer Johan Neyts Olivier Hantz Patrick Soussan Serban Morosan Dina Kremsdorf |
| author_facet |
Nicolas Brezillon Marie-Noëlle Brunelle Hélène Massinet Eric Giang Céline Lamant Lucie DaSilva Sophie Berissi Jacques Belghiti Laurent Hannoun Gherard Puerstinger Eva Wimmer Johan Neyts Olivier Hantz Patrick Soussan Serban Morosan Dina Kremsdorf |
| author_sort |
Nicolas Brezillon |
| title |
Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice. |
| title_short |
Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice. |
| title_full |
Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice. |
| title_fullStr |
Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice. |
| title_full_unstemmed |
Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice. |
| title_sort |
antiviral activity of bay 41-4109 on hepatitis b virus in humanized alb-upa/scid mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/ce3067c018d44286925e45fb1cf480f7 |
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