The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer.

@article{Yang2020TheBS,
  title={The broad spectrum antiviral ivermectin targets the host nuclear transport importin $\alpha$/$\beta$1 heterodimer.},
  author={Sundy N. Y. Yang and Sarah C Atkinson and Chunxiao Wang and Alexander Lee and Marie A. Bogoyevitch and Natalie A. Borg and David Andrew Jans},
  journal={Antiviral research},
  year={2020},
  pages={
          104760
        }
}

Tables from this paper

Antivirals that target the host IMPα/β1-virus interface

Preliminary results for randomised clinical trials (RCTs) as well as observational/retrospective studies are consistent with ivermectin affording clinical benefit, and the results from rigorous RCTs will help determine the therapeutic potential of the IMPα/β1-virus interface as a target for antiviral development.

Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?

The case for ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2 is discussed.

The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?

  • D. JansK. Wagstaff
  • Biology, Medicine
    Biochemical and Biophysical Research Communications
  • 2020

Inhibition of Human Adenovirus Replication by the Importin α/β1 Nuclear Import Inhibitor Ivermectin

ivermectin inhibits HAdV-C5 early gene transcription, early and late protein expression, genome replication, and production of infectious viral progeny, and provides a mechanistic underpinning for its mode of action as an inhibitor of cellular Imp-α/β1-mediated nuclear import.

Suppression of classical nuclear import pathway by importazole and ivermectin inhibits rotavirus replication.

In vitro studies revealed that treatment of ivermectin and importazole resulted in reduced synthesis of viral proteins, diminished production of infectious virus particles, and decrease in viroplasm-positive cells, and Mechanistic study proved that both drugs perform antirotavirus activity by inhibiting the function of importin-β1.

Ivermectin effectively inhibits hepatitis E virus replication, requiring the host nuclear transport protein importin α1

It is shown that ivermectin effectively inhibits infection with hepatitis E virus genotypes 1 and 3 in a range of cell culture models, including hepatic and extrahepatic cells, and that long-term treatment showed no clear evidence of the development of drug resistance.

Ivermectin Inhibits Bovine Herpesvirus 1 DNA Polymerase Nuclear Import and Interferes With Viral Replication

Treatment of cells with Ivermectin, an anti-parasitic drug which has been recently identified as an inhibitor of importin α/β-dependent nuclear transport, reduced UL42 nuclear import and specifically reduced BoHV-1 replication in a dose-dependent manner, while virus attachment and entry into cells were not affected.

In silico identification of ivermectin as an influenza A virus nuclear export protein inhibitor

The possibility of exploring ivermectin as a potential IAV NEP protein blocker is highlighted, which could be an important therapeutic strategy in the treatment of influenza.

How SARS-CoV-2 and Other Viruses Build an Invasion Route to Hijack the Host Nucleocytoplasmic Trafficking System

The viral factors and the host factors involved in the nuclear import and export of viral components and several drugs that target the host nuclear transport machinery are reviewed and their feasibility for use in antiviral treatment is discussed.
...

References

SHOWING 1-10 OF 84 REFERENCES

Novel Flavivirus Antiviral That Targets the Host Nuclear Transport Importin α/β1 Heterodimer

GW5074 not only inhibits IMPα binding to IMPβ1, but can dissociate preformed IMPα/β1 heterodimer, through targeting the IMPα armadillo (ARM) repeat domain to impact IMPα thermal stability and α-helicity.

Nucleocytoplasmic Trafficking of Dengue Non-structural Protein 5 as a Target for Antivirals.

DENV non-structural protein 5 (NS5) traffics into and out of the host cell nucleus/nucleolus, being observed in the nucleus, although to differing extents, very early in infection in the case of all 4 DENV serotypes; with results from both reverse genetics and inhibitor studies indicating that this trafficking is critical to DENV infection.

Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus

It is established for the first time that ivermectin has potent antiviral activity towards both HIV-1 and dengue virus, both of which are strongly reliant on importin α/β nuclear import, with respect to the HIV- 1 integrase and NS5 (non-structural protein 5) polymerase proteins respectively.

Recognition by host nuclear transport proteins drives disorder-to-order transition in Hendra virus V

It is shown that specific inhibitors of nuclear transport prevent interaction with host transporters, and reduce HeV infection, and potential use of compounds targeting nuclear transport, such as the FDA-approved agent ivermectin, as anti-HeV agents are considered.

A nuclear transport inhibitor that modulates the unfolded protein response and provides in vivo protection against lethal dengue virus infection.

4-HPR is a novel antiviral that modulates the unfolded protein response, effective against DENV1-4 at concentrations achievable in the plasma in a clinical setting, and provides protection in a lethal mouse model.

Molecular dissection of an inhibitor targeting the HIV integrase dependent preintegration complex nuclear import

Significantly, budesonide or its analogue flunisolide were able to effect a significant reduction in the presence of specific nuclear forms of the HIV DNA (2‐LTR circles), suggesting that the inhibitors work though blocking IN, and potentially PIC, nuclear import.
...