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The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?
David A Jans1, Kylie M Wagstaff2
1Nuclear Signaling Lab., Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.
Abstract:
FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) α/β1 heterodimer, and recently demonstrated its ability to bind directly to IMPα to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins. Cell culture experiments have shown robust antiviral action towards a whole range of viruses, including HIV-1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Close to 70 clinical trials are currently in progress worldwide for SARS-CoV-2. Although few of these studies have been completed, the results that are available, as well as those from observational/retrospective studies, indicate clinical benefit. Here we discuss the case for ivermectin as a host-directed broad-spectrum antiviral agent, including for SARS-CoV-2.
Insights
Ivermectin, FDA-approved for parasitic infections, shows broad-spectrum antiviral potential. It inhibits viral protein import into the cell nucleus, demonstrating efficacy against numerous viruses including SARS-CoV-2.
Area of Science:
- Virology
- Drug Discovery
- Molecular Biology
Background:
- Ivermectin is an FDA-approved antiparasitic drug.
- Recent research highlights its potential antiviral properties.
- Its mechanism involves inhibiting nuclear import of viral proteins.
Purpose of the Study:
- To investigate ivermectin's broad-spectrum antiviral activity.
- To elucidate the mechanism of ivermectin's antiviral action.
- To discuss ivermectin as a host-directed antiviral agent for SARS-CoV-2.
Main Methods:
- High-throughput compound library screening.
- In vitro cell culture experiments.
- Analysis of viral protein-host importin interactions.
Main Results:
- Ivermectin inhibits Human Immunodeficiency Virus-1 (HIV-1) integrase recognition by importin α/β1.
- It binds directly to importin α, altering its conformation and blocking nuclear import.
- Demonstrated antiviral activity against HIV-1, dengue, Zika, West Nile Virus, SARS-CoV-2, and others in cell culture.
Conclusions:
- Ivermectin acts as a host-directed antiviral by interfering with nuclear import pathways.
- It exhibits broad-spectrum efficacy against a wide range of RNA and DNA viruses.
- Clinical trials are ongoing to evaluate its therapeutic benefit for SARS-CoV-2 infections.
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