Catherine Fauvelle1,2, Melanie Lambotin1,2,3, Laura Heydmann1,2, Ekambaranellore Prakash4, Sunil Bhaskaran4, Mohan Vishwaraman4, Thomas F Baumert5,6,7, Christiane Moog8,9,10. 1. Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France. 2. Université de Strasbourg, Strasbourg, France. 3. Association ORACLE, Centre d'Oncologie de Gentilly, Nancy, France. 4. Indus Biotech Pvt Ltd, Pune, India. 5. Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France. Thomas.Baumert@unistra.fr. 6. Université de Strasbourg, Strasbourg, France. Thomas.Baumert@unistra.fr. 7. Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Thomas.Baumert@unistra.fr. 8. Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France. c.moog@unistra.fr. 9. Université de Strasbourg, Strasbourg, France. c.moog@unistra.fr. 10. Inserm, U1109, Fédération de Médecine Translationnelle (FMTS), Strasbourg, France. c.moog@unistra.fr.
Abstract
BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. Although direct-acting antivirals can cure the large majority of treated patients, important limitations remain, including treatment failure and high costs precluding access to therapy in resource-limited settings. We report herein the anti-HCV effects of IND02, a procyanidin type A molecule, isolated and characterized from cinnamon. METHODS AND RESULTS: Using cellculture-derived HCV (HCVcc), HCV pseudoparticles (HCVpp), and subgenomic replicons, we demonstrated that IND02 markedly and dose-dependently inhibited HCV cell entry. Kinetic assays demonstrated that IND02 inhibits HCV entry most likely at a postbinding step. Experiments performed using primary human hepatocytes confirmed inhibition of HCV entry by IND02, demonstrating the functional impact in the most physiological cell-based system for studying HCV-host interactions. CONCLUSIONS: The natural compound IND02 exhibits potent HCV cell entry inhibition and provides a novel perspective for development of a low-cost antiviral for treatment of HCV infection.
BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. Although direct-acting antivirals can cure the large majority of treated patients, important limitations remain, including treatment failure and high costs precluding access to therapy in resource-limited settings. We report herein the anti-HCV effects of IND02, a procyanidin type A molecule, isolated and characterized from cinnamon. METHODS AND RESULTS: Using cellculture-derived HCV (HCVcc), HCV pseudoparticles (HCVpp), and subgenomic replicons, we demonstrated that IND02 markedly and dose-dependently inhibited HCV cell entry. Kinetic assays demonstrated that IND02 inhibits HCV entry most likely at a postbinding step. Experiments performed using primary human hepatocytes confirmed inhibition of HCV entry by IND02, demonstrating the functional impact in the most physiological cell-based system for studying HCV-host interactions. CONCLUSIONS: The natural compound IND02 exhibits potent HCV cell entry inhibition and provides a novel perspective for development of a low-cost antiviral for treatment of HCV infection.
Authors: Isabel Fofana; Samira Fafi-Kremer; Patric Carolla; Catherine Fauvelle; Muhammad Nauman Zahid; Marine Turek; Laura Heydmann; Karine Cury; Juliette Hayer; Christophe Combet; François-Loïc Cosset; Thomas Pietschmann; Marie-Sophie Hiet; Ralf Bartenschlager; François Habersetzer; Michel Doffoël; Zhen-Yong Keck; Steven K H Foung; Mirjam B Zeisel; Françoise Stoll-Keller; Thomas F Baumert Journal: Gastroenterology Date: 2012-04-10 Impact factor: 22.682
Authors: Thomas Pietschmann; Artur Kaul; George Koutsoudakis; Anna Shavinskaya; Stephanie Kallis; Eike Steinmann; Karim Abid; Francesco Negro; Marlene Dreux; Francois-Loic Cosset; Ralf Bartenschlager Journal: Proc Natl Acad Sci U S A Date: 2006-05-01 Impact factor: 11.205
Authors: Jan M Pestka; Mirjam B Zeisel; Edith Bläser; Peter Schürmann; Birke Bartosch; Francois-Loïc Cosset; Arvind H Patel; Helga Meisel; Jens Baumert; Sergei Viazov; Kay Rispeter; Hubert E Blum; Michael Roggendorf; Thomas F Baumert Journal: Proc Natl Acad Sci U S A Date: 2007-03-28 Impact factor: 11.205
Authors: Moussa Bamba; Simon Bordage; Marie-Emmanuelle Sahuc; Sophie Moureu; Jennifer Samaillie; Vincent Roumy; Peggy Vauchel; Krasimir Dimitrov; Yves Rouillé; Jean Dubuisson; Fézan Honora Tra Bi; Karin Séron; Sevser Sahpaz Journal: Front Pharmacol Date: 2022-01-28 Impact factor: 5.810