# Taking aim at HBV eradication using novel NRTIs and Capsid effectors

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $568,676

## Abstract

PROJECT SUMMARY
 More than 350 million people are chronically infected by Hepatitis B Virus (HBV) and are at high risk for
developing cirrhosis and liver cancer. Current drugs do not cure HBV and do not target covalently closed-
circular DNA (cccDNA), which has been linked to viral persistence in HBV-infected hepatocytes. Moreover,
current therapies require lifetime treatment to suppress viral load and prolonged treatments lead to the
development of drug resistant strains. Finally, there is only a single family of directly acting antiretrovirals
(DAAs) that can block HBV infection, preventing meaningful combination therapies equivalent to formidable
highly active antiretroviral therapies (HAART) that tipped the scales in the fight against AIDS.
 The long term goal of this work is to develop HBV therapies that lead to HBV eradication. It is hypothesized
that combinations of novel, potent, and selective inhibitors of HBV can lead to more efficient suppression of
reverse transcription (RT), lack of cross-resistance, synergistic mechanism of action and depletion of cccDNA,
which in turn could lead to the eradication of HBV. Towards that end, this project focuses on the development
of leads that target viral replication by capsid assembly effectors (CAEs) and highly potent novel NRTIs. The
following specific aims are proposed:
Specific Aim 1: Characterize the potency determinants of novel highly active NRTIs.
Specific Aim 2: Discovery and characterization of novel capsid assembly effectors (CAEs)
Specific Aim 3: Characterization of novel NRTI and CAE combinations
 These studies will identify promising leads for the development of future anti-HBV drugs from two different
classes and will help design novel combinations that should efficiently suppress cccDNA by targeting Cp and
include highly potent HBV NRTIs towards a sustained virological response that could lead to HBV eradication.

## Key facts

- **NIH application ID:** 9918244
- **Project number:** 5R01AI121315-06
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Stefan G Sarafianos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $568,676
- **Award type:** 5
- **Project period:** 2017-11-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918244

## Citation

> US National Institutes of Health, RePORTER application 9918244, Taking aim at HBV eradication using novel NRTIs and Capsid effectors (5R01AI121315-06). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9918244. Licensed CC0.

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