期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 538, 期 -, 页码 163-172出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.10.042
关键词
Ivermectin; Antiviral; SARS-CoV-2; COVID-19; Dengue virus; Zika virus
资金
- National Health and Medical Research Council Australia [APP1002486/APP1103050]
- National Breast Cancer Foundation [ECF-17-007]
Ivermectin, originally approved for parasitic indications, has gained attention in recent years as a potential antiviral agent. Studies have shown its ability to inhibit a range of viruses, including HIV-1, dengue, Zika, and SARS-CoV-2. Numerous clinical trials are currently underway, with preliminary results indicating clinical benefits.
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) alpha/beta 1 heterodimer, and recently demonstrated its ability to bind directly to IMP alpha 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. (C) 2020 Published by Elsevier Inc.
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