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.
- 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
Stuart Le Grice (NCI), Fardokht Abulwerdi (NCI), Peter Stockley (University of Leeds), Reidun Twarock (University of York)
- U.S. Provisional: U.S. Provisional Patent Application Number 62/685,145 , Filed 14 Jun 2018