Novel Small Molecules that Inhibit Hepatitis B Virus Replication by Targeting Packaging of Pre-genomic RNA

Hepatitis B virus (HBV) is the smallest animal-infecting DNA virus with a compact 3.2 kDa genome that encodes seven proteins contained in four overlapped genes. Its small genome size and limited coding capacity make finding effective anti-HBV therapies difficult. Current treatment strategies for chronic HBV include liver transplantation or broad-spectrum nucleos(t)ide analogs including Lamivudine and Tenofovir, which are used to achieve viral suppression. Unfortunately, long-term administration of these nucleos(t)ide analogs is costly and can lead to the development of resistance mutations. While vaccines exist for HBV, there is a risk of vaccine escape mutations occurring due to complete overlap of the surface antigen proteins inside the gene for the HBV polymerase protein. The threat of a vaccine-immune virus entering the general population warrants continued studies to uncover novel targets for viral suppression.

Researchers at the National Cancer Institute (NCI), in collaboration with the University of Leeds and the University of York, have investigated a novel, previously unidentified HBV RNA packaging signal (PS1). Furthermore, the researchers have identified small molecules capable of specifically recognizing PS1 in HBV pre-genomic RNA (pgRNA). These small molecules have proven effective at suppressing HBV replication with little to no toxicity. Compared to some clinically approved anti-HBV drugs, these molecules are significantly more inhibitory. This discovery provides, for the first time, small molecules that can be used to inhibit HBV replication by targeting an important packaging signal of its pgRNA. These can be used either alone or in combination with nucleoside/nucleotide analogs currently being used to treat HBV infections.

Potential Commercial Applications: Competitive Advantages:
  • Hepatitis B virus (HBV) therapy
  • Small molecules effective at suppressing HBV virus replication with little to no toxicity
  • Only known small molecules that inhibit HBV replication by targeting pre-genomic RNA

Development Stage:
Discovery (Lead Identification)


Stuart Le Grice (NCI)  ➽ more inventions...

Fardokht Abulwerdi (NCI)  ➽ more inventions...

Peter Stockley

Reidun Twarock

Intellectual Property:
Application No. 62/685,145

Collaboration Opportunity:

Licensing and research collaboration

Licensing Contact:
John Hewes, Ph.D.
Phone: 240-276-5515

OTT Reference No: E-062-2018
Updated: Nov 14, 2018