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

Abstract

The small molecule macrocyclic lactone ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its apparent exciting potential as an antiviral. It was identified in a high-throughput chemical screen as inhibiting recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host heterodimeric importin (IMP) α/β1 complex, and has since been shown to bind directly to IMPα to induce conformational changes that prevent its normal function in mediating nuclear import of key viral and host proteins. Excitingly, cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Phase III human clinical trials have been completed for DENV, with >50 trials currently in progress worldwide for SARS-CoV-2. This mini-review discusses the case for ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.

• Authors: David A Jans, Kylie M Wagstaff
• Journal: Cells (Cells) Vol. 9 Issue 9 (09 15 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 32942671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antiviral Agents
• HIV Integrase Inhibitors
• Ivermectin
• HIV Integrase

Topics

• Animals
• Antiviral Agents (pharmacology)
• Betacoronavirus (drug effects)
• COVID-19
• Cell Line
• Chlorocebus aethiops
• Coronavirus Infections (drug therapy)
• Dengue (drug therapy)
• Dengue Virus (drug effects)
• HIV Infections (drug therapy)
• HIV Integrase (drug effects)
• HIV Integrase Inhibitors (pharmacology)
• HIV-1 (drug effects)
• Humans
• Ivermectin (pharmacology)
• Pandemics
• Pneumonia, Viral (drug therapy)
• SARS-CoV-2
• Vero Cells
• Zika Virus (drug effects)
• Zika Virus Infection (drug therapy)