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.
Bulevirtide (Myrcludex B) is a NTCP inhibitor, a linear lipopeptide of 47 amino acids. Bulevirtide inhibits HBV and HDV entry into liver cells, blocks HBV infection in hepatocytes, and participates in HBV transcriptional suppression. Bulevirtide can be used in HDV infection and compensated cirrhosis research[1][2].
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].
Bulevirtide (2 μg/g, s.c. for everyday) prevents HBV spreading from infected human hepatocytes in uPA/SCID mice, hinders amplification of the cccDNA pool in initially infected hepatocytes[4].
Bulevirtide (2 μg/g/d, s.c. for 3 weeks) blocks HBV cell entry in uPA/SCID mice through addressing the hepatocyte component rather than affecting virion productivity within the infected hepatocyte or the half-life of these cells[4].
Bulevirtide (5 μg,s.c., twice a day for 4 days) blocks upregulation of NTCP mediated-HBV replication in C57BL/6 mice as a replication inhibitor[5].
| Animal Model: | HBV infected uPA/SCID mice[3] |
| Dosage: | 2 μg/g |
| Administration: | subcutaneous injection, for everyday |
| Result: | Blocked the viremia and and HBsAg concentrations.
Maintained the cell death rate and proliferated hepatocytes amount.
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[1] Liu, Hongtao et al. “Structure of antiviral drug bulevirtide bound to hepatitis B and D virus receptor protein NTCP.” Nature Communications 22 1 (2024).
