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

Author:

King Cason R.1ORCID,Tessier Tanner M.1,Dodge Mackenzie J.1,Weinberg Jason B.23ORCID,Mymryk Joe S.145ORCID

Affiliation:

1. Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

2. Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

3. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA

4. Department of Oncology, University of Western Ontario, London, Ontario, Canada

5. London Regional Cancer Program and Lawson Health Research Institute, London, Ontario, Canada

Abstract

Human adenoviruses (HAdVs) represent a ubiquitous and clinically important pathogen without an effective antiviral treatment. HAdV infections typically cause mild symptoms; however, individuals such as children, those with underlying conditions, and those with compromised immune systems can develop severe disseminated disease. Our results demonstrate that ivermectin, an FDA-approved antiparasitic agent, is effective at inhibiting replication of several HAdV types in vitro . This is in agreement with the growing body of literature suggesting ivermectin has broad antiviral activity. This study expands our mechanistic knowledge of ivermectin by showing that ivermectin targets the ability of importin-α (Imp-α) to recognize nuclear localization sequences, without effecting the Imp-α/β1 interaction. These data also exemplify the applicability of targeting host factors upon which viruses rely as a viable antiviral strategy.

Funder

Gouvernement du Canada | Canadian Institutes of Health Research

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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