Efficient Inhibition of Hepatitis B Virus Infection by a preS1-binding Peptide

Abstract

Entry inhibitors are promising novel antivirals against hepatitis B virus (HBV) infection. The existing potential entry inhibitors have targeted the cellular receptor(s). In this study, we aim to develop the first entry inhibitor that inhibits HBV infection via targeting viral particles. The preS1 segment of the large envelope glycoprotein of HBV is essential for virion attachment and infection. Previously, we obtained a preS1-binding short peptide B10 by screening a phage display peptide library using the N-terminal half of preS1 (residues 1 to 60, genotype C). We report here that by means of concatenation of B10, we identified a quadruple concatemer 4B10 that displayed a markedly increased preS1-binding activity. The main binding site of 4B10 in preS1 was mapped to the receptor binding enhancing region. 4B10 blocked HBV attachment to hepatic cells and inhibited HBV infection of primary human and tupaia hepatocytes at low nanomolar concentrations. The 4B10-mediated inhibition of HBV infection is specific as it did not inhibit the infection of vesicular stomatitis virus glycoprotein pseudotyped lentivirus or human immunodeficiency virus type 1. Moreover, 4B10 showed no binding activity to hepatic cells. In conclusion, we have identified 4B10 as a promising candidate for a novel class of HBV entry inhibitors.

hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs

“…Myr-preS1 2-47 and 4B10, the peptide HBV entry inhibitors, exhibited concentration-dependent inhibition of HBsAg and HBeAg secretion and HBV DNA in the supernatants as higher concentration of inhibitors significantly reduced antigens/virion secretion compared with the lower concentration although there is a plateau, with a half maximal inhibitory concentration (IC 50 ) of 0.5–1 nM (Fig. 4A-C), which matches the reported data regarding HBV infection in the PHH model (23). Lamivudine, an inhibitor of HBV replication, also exhibited concentration-dependent inhibition of HBsAg and HBeAg secretion and HBV DNA in the supernatants, with an IC 50 of ~50 nM.…”

“…Lamivudine, Myr-preS1 2-47 and 4B10 are well-characterized inhibitors of HBV replication and/or HBV entry (23–25) and were tested in HBV-infected hNTCP-complemented PPHs in the present study. The three inhibitors were non-cytotoxic to hNTCP-complemented PPHs (Fig.…”

Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride

“…The similarity is depicted in the left panel of this figure. It triggers an extremely effective "binding competitive" approach to SARS-CoV-2 inactivation which stems from several successful other examples such as Hepatitis B [42] and Influenza A [43]. The strong antiviral effect of eluted (gaseous) NH3 is due to its penetration of the virions and its reaction with the RNA backbone.…”

Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM–HopQ Interaction and Subsequent CagA Translocation

“…One approach that has proven successful in the past is the use of peptides to block pathogen binding. This has been demonstrated in approaches targeting viruses, such as Hepatitis B [24], human cytomegalovirus [25], influenza virus [26] and others [27], and, more recently, bacteria such as Mycobacterium tuberculosis [28]. Another approach is the use of antibodies to block the host-pathogen interaction [3], as well as nanobodies that overcome the limitations of traditional monoclonal antibodies and peptides as therapeutics [29,30].…”