Bulevirtide (BLV), the first-in-class entry inhibitor, is a 47-amino acid synthetic liner lipopeptide derived from the preS1 domain of the HBV large surface that targets the NTCP, the entry receptor for HBV/HDV. By blocking this receptor, new infections are prevented, and infected hepatocytes are replaced by naive cells that will be protected from infection. Consequently, viral spread in the liver is prevented.
The sequence of Bulevirtide (BLV) is derived from that of preS1 from HBV genotype C (residues Gly2-Gly48) with a shortening of the 11 additional N-terminal amino acids and one amino acid substitution, Gln46Lys. BLV exhibits a remarkably high inhibitory constant (IC50?=?140 pM) against HBV and HDV in primary human hepatocytes and HepaRG cells. BLV has also been demonstrated to inhibit the NTCP-mediated uptake of bile salts but at an IC50 in the nanomolar range[1].
