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.