FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro

Although several clinical trials are now underway to test possible therapies, the worldwide 18 response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.

Ivermectin is an FDA-approved broad spectrum anti-parasitic agent1 that in 27 recent years we,along with other groups, have shown to have anti-viral activity against a broad range of viruses2-5 in vitro. Originally identified as an inhibitor of interaction between the human immunodeficiency virus-1 (HIV-1) integrase protein (IN) and the importin (IMP) a/b1 heterodimer responsible for IN nuclear import6, Ivermectin has since been confirmed to inhibit IN nuclear import and HIV-1 replication5. Other actions of ivermectin have been reported7, but ivermectin has been shown to inhibit nuclear import of host (eg. 8, 9) and viral proteins, including simian virus SV40 large tumour antigen (T-ag) and dengue virus (DENV) non-structural protein 55, 6. Importantly, it has been demonstrated to limit infection by RNA viruses such as DENV 1-44, West Nile Virus10, Venezuelan equine encephalitis virus (VEEV)3 and influenza2, with this broad spectrum activity believed to be due to the reliance by many different RNA viruses on IMPa/b1 during infection11, 12. Ivermectin has similarly been shown to be effective against the DNA virus pseudorabies virus (PRV) both in vitro and in vivo, with ivermectin treatment shown to increase survival in PRV-infected mice13. Efficacy was not observed for ivermectin against Zika virus (ZIKV) in mice, but the authors acknowledged that study limitations justified re-evaluation of ivermectin’s anti-ZIKV activity14. Finally, ivermectin was the focus of a phase III clinical trial in Thailand in 2014-2017, against DENV infection, in which a single daily oral dose was observed to be safe and resulted in a significant reduction in serum levels of viral NS1 protein, but no change in viremia or clinical benefit was observed.

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