Ivermectin in COVID-19 prevention and treatment – what does the science say?

The last two years have seen a pandemic of the coronavirus and the COVID-19 disease caused by this virus. As citizens find information about COVID-19 much easier and faster on the Internet, in recent months we have seen an unreliable and scientifically unproven statement that ivermectin can act on coronavirus and cure COVID-19, and we are witnessing many people voluntarily using it in the treatment of this disease. In this article, we want to look at the problems and justification of the use of the drug ivermectin for the prevention and treatment of COVID-19 in humans.

What is Ivermectin?

Ivermectin is a dihydro derivative of avermectin, a natural fermentation metabolite of the bacterium Streptomyces avermitilis. It belongs to the pharmacological group of broad-spectrum antiparasitic drugs. In veterinary practice it is used to treat certain parasitic diseases while in humans it is used for the treatment of parasitic diseases caused by internal and external parasites such as helminths, nematodes, mites and for skin diseases such as rosacea. In addition, ivermectin exhibits antiviral and anti-inflammatory effects and, due to its safety, affordability and availability, has been under investigation since the beginning of the coronavirus pandemic for its potential use in the treatment of COVID-19 disease caused by SARS-CoV-2 virus.

Does Ivermectin work on SARS-CoV-2?

Ivermectin is a drug approved for the treatment of parasitic infections as well as certain skin diseases in humans, but research on ivermectin in recent years has shown its antiviral activity in vitro against certain DNA and RNA viruses. The novel coronavirus, SARS-CoV-2, is a positively directed single-stranded RNA virus (+ ssRNA), and in vitro studies show that high concentrations of ivermectin have a potentially inhibitory effect on replication of this virus in cell cultures. The mechanism of action has not yet been fully investigated, but due to the similarity of this virus to the SARS-CoV virus studied, the carrier of the virus, the IMPα / β1 heterodimer, which transports it from the cytoplasm of the cell to the cell nucleus, is thought to be important in the inhibition of virus replication. IMPα / β1 transports the virus through a “tunnel” called the nuclear pore complex (NCP). After entering the cell nucleus, the virus begins to multiply and new viral particles form. It is believed that ivermectin in this case binds to the virus carrier and destabilizes it, so the carrier will not bind to the virus, it will not enter the nucleus and will not multiply, which leads to reduced spread of the infection. Moreover, in silico studies of ivermectin (in silico = drug studies performed virtually, by computer simulation) show that the drug could potentially inhibit a coronavirus enzyme called 3-chymotrypsin-like protease (3CLpro), which is important for generating viral proteins. Inhibition of this enzyme prevents the formation of new virus particles in the cell. Also, certain research shows that ivermectin can potentially inhibit the binding of the novel coronavirus to ACE2 receptors on human cells, preventing virus entry into cells, and reducing viral infection.

Justification of the use of Ivermectin to treat COVID-19

The available studies on ivermectin in the treatment of COVID-19 disease are mostly based on preclinical studies, which show potential antiviral activity against the novel coronavirus. However, these studies are only the beginning of research into ivermectin as a possible future drug for the treatment of coronavirus disease and they precede clinical trials. In addition, preclinical studies have shown some shortcomings, such as the use of much higher doses of ivermectin than the dose recommended for human use, which ranges from 0.15 to 0.2 mg / kg. Current clinical trials, studies on the impact of ivermectin in the treatment of COVID-19 disease in humans, are insufficient and mostly of low certainty, and only a few of these studies are considered high quality. Also, the results of the available clinical trials vary, and the studies themselves show some additional limitations. Therefore, regulatory bodies in the United States (FDA, WHO), Europe (EMA), as well as the Croatian HALMED, in conclusion, do not recommend the use of ivermectin for prevention or treatment of COVID-19 disease outside of clinical trials.

Ivermectin, a widely used antiparasitic drug and a drug that shows antiviral activity, has recently attracted the attention of many scientists, but also the public because of the possible effect on the novel coronavirus. Although available preclinical studies demonstrate its effect on SARS-CoV-2 virus, previous clinical studies on the effectiveness of ivermectin in the treatment of novel coronavirus disease are insufficient. In conclusion, currently available reliable evidence does not support the use of ivermectin for prevention or treatment of COVID-19 disease. Further research is needed to conclude whether the use of ivermectin is justified for prevention and treatment of the COVID-19 disease in humans.

Translated by: Antonio Ljulj