Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen

Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly effective against many microorganisms including some viruses. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in vivo studies over the past 50 years. Several studies reported antiviral effects of ivermectin on RNA viruses such as Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. Furthermore, there are some studies showing antiviral effects of ivermectin against DNA viruses such as Equine herpes type 1, BK polyomavirus, pseudorabies, porcine circovirus 2, and bovine herpesvirus 1. Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.

Ivermectin: a multifaced medication

Ivermectin has been used for several years to treat many infectious diseases in mammals. It has a good safety profile with low adverse effects when orally prescribed. Ivermectin was identified in late 1970s and first approved for animal use in 1981. Its potential use in humans was confirmed a few years later. Subsequently, William C. Campbell and Satoshi Ōmura who discovered and developed this medication received the 2015 Nobel Prize in Physiology or Medicine [1,2,3].

Studies revealed that ivermectin as a broad-spectrum drug with high lipid solubility possesses numerous effects on parasites, [1, 3] nematodes, arthropods, flavivirus, mycobacteria, and mammals through a variety of mechanisms. In addition to having antiparasitic and antiviral effects, this drug also causes immunomodulation in the host. Studies have shown its effect on inhibiting the proliferation of cancer cells, as well as regulating glucose and cholesterol in animals. Despite diverse effects of this medication, many of its underlying mechanisms are not yet known [4]. Of note, some of these effects may be secondary to toxic effects on cells (Fig. 1).