Ivermectin Inhibits HBV Entry into the Nucleus by Suppressing KPNA2

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I found this study interesting and wanted to share it. I had it summarised by ChatGPT to make it easier to understand. I would love to hear any comments you might have on this topic.

Ivermectin Inhibits HBV Entry into the Nucleus by Suppressing KPNA2

This study explores how ivermectin, a drug commonly used to treat parasitic infections, can inhibit hepatitis B virus (HBV) in liver cells. The research shows that ivermectin interferes with the virus’s ability to replicate and produce key viral markers, such as HBV DNA, HBsAg (a surface protein), and cccDNA (a stable form of viral DNA that allows the virus to persist in cells).

Key Points:

  1. Ivermectin’s Effects on HBV:

    • In both cancerous liver cells and normal human liver cells, ivermectin significantly reduces levels of viral markers like HBV DNA, HBsAg, and HBcrAg (another viral protein).
    • Importantly, ivermectin does not harm liver cells, indicating that it can suppress the virus without causing toxic side effects.

  2. Unique Mechanism of Action:

    • Unlike other antiviral drugs like entecavir (ETV) or cyclosporine A (CsA), ivermectin does not block HBV from entering cells or inhibit its reverse transcription (which is how the virus replicates its DNA).
    • Instead, ivermectin prevents the viral core protein HBc from reaching the nucleus of the cell. HBc plays a crucial role in viral replication. By stopping it from entering the nucleus, ivermectin disrupts the production of new viruses.

  3. Ivermectin Targets Specific Proteins:

    • The study identifies a group of proteins called importins, particularly KPNA2, that help HBV proteins enter the cell’s nucleus. Ivermectin blocks the movement of KPNA2 into the nucleus, which in turn stops the virus from reproducing.
    • Other importins (KPNA1, KPNA4, KPNA6) also play roles in HBV infection. Reducing the levels of these proteins lowers the virus’s ability to replicate, with KPNA2 being the most important target for ivermectin.

  4. Potential for Future Therapies:

    • The findings suggest that ivermectin might be useful in treating HBV because it works through a novel pathway, different from existing antiviral drugs. Since ivermectin specifically targets the importins that facilitate viral replication, it could become part of a new approach to HBV treatment, particularly for patients who don’t respond well to current therapies.

Conclusion:

Ivermectin shows promise as a potential treatment for hepatitis B by preventing the virus from entering the nucleus of liver cells, thereby halting its replication. This novel approach could offer an alternative to existing antiviral drugs and help reduce the persistence of HBV in infected individuals.

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Hi @Althaea,

Thanks for bringing this up for discussion.

The effect size of ivermectin on HBV in these in vitro models is relatively weak (about 2 fold decrease in some markers, less than that for new cccDNA formation).

The other point is that the doses of ivermectin used in this study are incredibly high (10 micromolar). This is around 70-fold higher than the maximum plasma concentration of any approved dosage of ivermectin (The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19 - PubMed).

As such, this study might give some detail into how the virus gets into the cell and what proteins it interacts with, but it is not likely that ivermectin will be a promising candidate for treatment of hep B.

Hope this helps,
Thomas