# HBV Capsid Effectors

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $531,433

## Abstract

PROJECT SUMMARY / ABSTRACT
Hepatitis B virus (HBV) remains a major worldwide public health challenge with 10-20 million
chronically infected individuals developing cirrhosis, characterized by a decline and loss of liver function
with a significantly decreased quality of life and a high mortality rate. While current therapies effectively
control the virus with few side effects, they do not cure since none target the HBV covalently closed-
circular DNA (cccDNA; associated with viral persistence). Our innovative approach targets capsid
assembly which is essential for replication, as DNA synthesis from cccDNA occurs exclusively within
the capsid encoded particle. Therefore, the focus of this proposal is on developing small molecules
targeting disruption of capsid formation which could ultimately impact cccDNA stability and/or formation
and also reduce duration of treatment in HBV infected persons. We are developing a novel class of
Capsid Assembly Effectors (CAE) that target capsid formation (glyoxamide derivatives). Recently, we
have identified a highly potent “lead” compound IV with selective activity at 3 nM. The proposed
specific AIMS will systematically define the pre-clinical parameters (including activity, toxicity, stability,
oral bioavailability, capsid binding interaction) of this novel class of CAE: AIM 1: to chemically optimize
and characterize a unique series of glyoxamide CAE, including our “lead” compound IV; AIM 2: to
structurally, biochemically, and biologically characterize novel CAE binding interaction with HBV
capsid.; and AIM 3: to determine pharmacokinetics (PK) and efficacy of novel CAE and combination
regimens in two different mouse models for HBV infection. Results from these studies will validate our
novel class of small molecule CAE, which when combined with other modalities (e.g., nucleoside
analogs) could provide preclinical “proof of concept” towards a novel therapeutic strategy with reduced
treatment duration and a functional cure for HBV infection.

## Key facts

- **NIH application ID:** 9926214
- **Project number:** 5R01AI132833-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Raymond Felix Schinazi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $531,433
- **Award type:** 5
- **Project period:** 2017-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926214

## Citation

> US National Institutes of Health, RePORTER application 9926214, HBV Capsid Effectors (5R01AI132833-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9926214. Licensed CC0.

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