Abstract: cells Review Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal? David A. Jans 1, * 1 2 * and Kylie M. Wagstaff 2 Nuclear Signaling Lab., Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Monash, Victoria 3800, Australia Cancer Targeting and Nuclear Therapeutics Lab., Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Monash, Victoria 3800, Australia; Kylie.Wagstaff@monash.edu Correspondence: David.Jans@monash.edu; Tel.: +61-404-679-865 Received: 8 August 2020; Accepted: 9 September 2020; Published: 15 September 2020



 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. Keywords: ivermectin; antiviral; SARS-CoV-2; COVID-19; flavivirus; dengue virus; Zika virus