Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

HBV Capsid Effectors

Award Number: R01AI132833
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

HBV Capsid Effectors - PROJECT SUMMARY/ABSTRACT Despite the availability of an effective vaccine, epidemiologic data estimates about 2 billion people globally are infected with hepatitis B virus (HBV). Approximately 350 million people are chronic HBV carriers and at high risk for the development of hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Current anti-HBV treatment options suppress the virus but do not eliminate the virus, requiring costly lifetime therapy. All FDA approved therapeutic approaches fail to target the HBV covalently closed-circular DNA (cccDNA; associated with viral persistence) or the virus capsid which is essential for virus proliferation. Our approach in this application is to target capsid assembly, which is essential for replication, as DNA synthesis from cccDNA occurs exclusively within the capsid encoded particle. HBV core proteins (Cp) constitute the subunits in viral capsid assembly and Capsid Assembly Modulators (CAM) accelerate the kinetics of capsid assembly whereby they prevent pol- pgRNA complex encapsidation and block HBV replication. CAMs also interfere with cccDNA transcription/de novo formation during early steps of infection. As part of our ongoing HBV CAM discovery program NIH- supported over the last 4 years, we have been successful in developing several highly potent (sub-micromolar) class II CAMs with one of our lead compounds entering phase 1 clinical trials in October 2020. However, there are numerous hurdles that could derail our efforts towards FDA approval. Here, we describe for the first time a novel class of homo or hetero-dimer CAM displaying selective anti-HBV activity in culture in the picomolar range. Because a dimeric structure linking two CAM moieties can interact with two distinct sites of one capsid or eventually connect two (or more) capsids together, we hypothesized that these compounds would have a more profound impact on HBV capsid assembly than known class I or II CAMs. Based on the potency and the unique mode of action (MoA) we termed our new compounds as “class III” CAMs. We propose to evaluate these class III CAMs by pursuing three specific aims: 1) To chemically optimize and characterize a unique series of CAM homo/heterodimers made from novel monomers; 2) To characterize (structurally, biochemically, and biologically) novel CAM homo/heterodimer binding interaction with HBV capsid; 3) To determine pharmacokinetics (PK) and in vivo efficacy of novel CAM homo and heterodimers. Novel homo and heterodimers will be synthesized and evaluated to reach maximum potency and drug-like properties. To differentiate our compounds from existing class I and II CAMs, we will characterize structural and dynamical effects of our new CAMs by determining a) their effect on the morphology of HBV capsids and their localization within cells, b) binding to HBV wild-type and known mutant Cp, c) resistance profile and activity against major CAM resistant HBV strains and d) intra- or inter-capsid connections. Results from the proposed studies will validate our novel class III CAM, which, when combined with other modalities will provide pre-clinical proof of concept towards a novel therapeutic strategy to eliminate HBV while reducing treatment duration and progression to HCC.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $676,194 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	9	2/12/2026	NON-COMPETING CONTINUATION	$676,194
														Subtotal = $676,194

Issue Date FY: 2025 ( Subtotal = $702,799 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	8	3/21/2025	NON-COMPETING CONTINUATION	$702,799
														Subtotal = $702,799

Issue Date FY: 2024 ( Subtotal = $632,520 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	7	7/3/2024	NON-COMPETING CONTINUATION	$632,520
														Subtotal = $632,520

Issue Date FY: 2023 ( Subtotal = $959,802 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	003	6	2/7/2023	NON-COMPETING CONTINUATION	$702,799
2023	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	005	5	2/16/2023	COMPETING CONTINUATION	$257,003
2023	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	5	11/21/2022	COMPETING CONTINUATION	-$31
2023	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	004	5	2/10/2023	COMPETING CONTINUATION	$819
2023	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	11/21/2022	COMPETING CONTINUATION	$31
2023	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	002	4	11/21/2022	NON-COMPETING CONTINUATION	-$819
														Subtotal = $959,802

Issue Date FY: 2022 ( Subtotal = $437,874 )
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	002	5	4/5/2022	COMPETING CONTINUATION	$31
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	3/18/2022	COMPETING CONTINUATION	$437,874
2022	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	4	4/5/2022	NON-COMPETING CONTINUATION	-$31
														Subtotal = $437,874

Issue Date FY: 2020 ( Subtotal = $531,433 )
2020	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	4	5/14/2020	NON-COMPETING CONTINUATION	$531,433
														Subtotal = $531,433

Issue Date FY: 2019 ( Subtotal = $537,558 )
2019	2019	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	3	5/6/2019	NON-COMPETING CONTINUATION	$537,558
														Subtotal = $537,558

Issue Date FY: 2018 ( Subtotal = $543,503 )
2018	2018	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	2	5/3/2018	NON-COMPETING CONTINUATION	$543,503
														Subtotal = $543,503

Issue Date FY: 2017 ( Subtotal = $563,003 )
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	5/29/2017	NEW	$563,003
														Subtotal = $563,003

Grand Total All Awards = $5,584,686

Top

All Categories

About

Search

Reports

Data Submission

Award Information

HBV Capsid Effectors

Award Number: R01AI132833

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer