Validation of novel in vitro systems for rapid detection of covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) to screen potential antivirals and toxicity profiles

Abstract

This project is intended to support the mobility of researchers in order to implement scientific and scholarly collaboration between Department of Gastroenterology - University of São Paulo School of Medicine and Center for AIDS Research, Laboratory of Biochemical Pharmacology (LOBP), Department of Pediatrics, Emory University School of Medicine for the study of liver diseases. The researchers have been collaborating since 1997 in the study of liver diseases, specifically in the evaluation of antivirals for chronic hepatitis B wild and mutant variants that resulted in a publication in a high impact journal (Journal of Clinical Investigation). Recently, in Brazil, the collaboration extended to co-supervision of Graduate and Medical students from University of São Paulo School of Medicine through PhD sandwich program and Graduation International Interchange program. Hospital das Clinicas from the University of São Paulo School of Medicine (HCFMUSP) is a Tertiary University Hospital and our Clinical Hepatology group is responsible for 12,000 consults per year. The Gastroenterology Department is in charge of education of Medical students, medical residents and post-graduate students. The project entitled "Focused pharmacogenomic panel for transplanted patients" is an important study on chronic hepatitis B and C patients who underwent orthotopic liver transplantation and was submitted to FAPESP and is being performed at HCFMUSP and the Gastroenterology Molecular Biology Laboratory (GastroLBM). The preliminary results will be discussed at the LOBP with experts in pharmacology under supervision of Prof. Raymond Schinazi who is a leader in antiviral discovery for HIV and viral hepatitis. During the previous two years, Prof. Ono and Prof. Bassit have been working on establishing a novel cell culture system and method to evaluate HBV wild type and mutants replication in order to study new antivirals and toxicities. The work resulted in two abstracts, the first accepted as an oral presentation in a prestigious European meeting (EASL 2018 e 2019). The manuscript of this work is under preparation. This is the minimum viable product that will enable the researchers to apply for NIH-FAPESP collaborative proposal. This work can progress to the development of novel in vitro systems for rapid detection of covalently-closed-circular DNA (ccc-DNA) of hepatitis B virus (HBV) to screen potential antivirals and toxicity profiles. Further collaboration for the study of liver diseases is already ongoing between the two universities. In particular, the discussion and planning of collaborative research and submission of proposal to the NIH - FAPESP. The collaboration extended to co-supervision of Graduate and Medical students from University of São Paulo School of Medicine through PhD sandwich program and Graduation International Interchange program. This demonstrates the strong affinity among the researchers and encourage further collaborations. This proposal will help to strengthen this International Collaboration between Department of Gastroenterology - University of São Paulo School of Medicine and Center for AIDS Research, Laboratory of Biochemical Pharmacology (LOBP), Department of Pediatrics, Emory University School of Medicine for the study of liver diseases. This international collaboration will present to academic personnel the opportunity to share experience, data and methods that will promote and support continuous improvement in quality of researches. (AU)