Therapeutic potential of ivermectin for COVID-19

Abstract

Background The aim of the present theoretical essay is to evaluate evidence published on the characteristics of the transcription of SARS-CoV-2 and explain the mechanism of action of ivermectin that may justify its therapeutic use in clinical practice for the treatment of COVID-19. Methods Laboratory studies, narratives, editorials and expert opinions on the subject were identified through a systematic search of the literature in the Medline/PubMed, Cochrane Library, Web of Science and Embase databases. Two blinded, independent reviewers selected studies published up to May 17, 2020 based on the eligibility criteria. Results The search of the databases led to the retrieval of 25 articles. After the different phases of the selection process, eight articles were included in the present review for the extraction of relevant data. The results suggest that ivermectin inhibits the viral replication of SARS-CoV-2 through the action of the hypoxia-inducible factor (HIF-1α) and consequent destabilization of importin α/β1 proteins. Conclusions Ivermectin inhibits the viral replication of SARS-CoV-2. Laboratory and clinical studies are needed to provide more evidence in terms of the best posology and possible associations with other drugs for combatting COVID-19.

Potential therapeutic effects of Ivermectin in COVID-19

“…Recent research has shown the strong antiviral properties of Ivermectin by inhibiting the replication of some RNA viruses in vitro . 33,34 Ivermectin is selectively concentrated in the pulmonary tissue, about 3 times more than the plasma concentration, and remains in the pulmonary tissue for a long time. 35 There is convincing evidence showing the therapeutic potential of Ivermectin for treating COVID-19.…”

“…103 Based on such evidence, it was suggested that Ivermectin has the potential to inhibit the SARS-CoV-2 replication and the cytokine-mediated pro-inflammatory response through blocking the formation of HIF-1α and IMP α/β1 complex. 34…”

“…95 Furthermore, there is also evidence that shows Ivermectin may exert the antiviral activity through inhibiting the formation of the host IMP-α/hypoxia-inducible factor 1-alpha (HIF-1α) complex. 34 HIF-1α is a subunit of a heterodimeric transcription factor that responds to the reduction of oxygen levels in the cellular environment or hypoxia, and adapts the cellular response to oxygen availability. [98][99][100] Through the virus-mediated activation of HIF-1α, the inflammatory response is exacerbated in severe cases of COVID-19 disease.…”

Features of Pathobiology and Clinical Translation of Approved Treatments for Coronavirus Disease 2019

“…Reduction of viral loads in COVID-19 patients treated with some antiviral agents that can inhibit the binding of SARS-CoV-2 to host cells was found in various phases of clinical trials, indicating the inhibitory effect of these molecules on viral envelope proteins and their host cell receptors/co-receptors [ 31 , 32 ]. These are including antiviral drugs (ivermectin), neutralizing monoclonal antibodies (bamlanivimab and etesevimab), recombinant human monoclonal antibodies (casirivimab, imdevimab, and sotrovimab), and convalescence plasma [ 33 ]. At the beginning of the pandemic, several studies reported data on the antiviral activity of ivermectin, hydroxychloroquine alone, or in combination with azithromycin against SARS-CoV-2 [ 34 , 35 , 36 ].…”

COVID-19 therapy: What weapons do we bring into battle?

“…Thus far, data indicate ivermectin is useful at the early stages of the disease, even the epidemiologic profile of COVID-19 shows significant differences regarding the age of patients for the affected countries and patients with comorbidity. 278 Therefore, large scale randomized clinical trials are necessary to standardize clinical, laboratory and image evaluations, as well as combined drug therapy with vitamins and zinc, for example. 279 Financially, ivermectin is inexpensive and its doses and protocols are well established for different purposes.…”