Broad-spectrum activity of bulevirtide against clinical isolates of HDV and recombinant pan-genotypic combinations of HBV/HDV

Background and AimsBulevirtide (BLV) is a small lipopeptide agent that specifically binds to the NTCP bile salt transporter HBV/HDV receptor on surface of human hepatocytes inhibits HDV HBV entry. As satellite virus HBV, virions are formed after assembly RNA with envelope proteins (HBsAg). Because both viruses exist as eight different genotypes, this creates potential for high diversity in combinations.To investigate sensitivity various combinations genotypes BLV, clinical laboratory strains were assessed.MethodsFor lab strains, envelopes from A through H combined 1 8 co-transfection assays. Clinical plasma isolates obtained studies academic collaborations maximize tested.ResultsThe mean BLV 50% effective concentration against ranged 0.44 nM 0.64 nM. Regardless showed similar sensitivities values 0.2 0.73 nM.ConclusionsThese data support use patients infected any genotypes.Impact ImplicationsThis study describes potent activity multiple spanning all A-H/1-8 genotype most diverse collection samples tested date, including less frequently observed clinic. Overall, displayed vitro nanomolar BLV. This broad-spectrum antiviral has direct implications simplified treatment patient HDV, regardless supports new 2023 EASL practice guidelines recommend CHD.