Ivermectin: a mini-review.

Introduction: Avermectins are common antiparasitic drugs, derived from Streptomyces bacteria that exhibit activity against arthropods and nematodes. Ivermectin, an avermectin derivative, is used as a treatment for parasitic infections in humans and domesticated animals.Discussion: Ivermectin's mechanism of action involves binding to ligand-gated ion channel receptors including glutamate, GABA, and glycine, resulting in parasitic paralysis and death. Due to varying expression of these ion channel receptors in vertebrate species, ivermectin toxicity is rarely reported in mammals. Ivermectin is also a substrate for P-glycoprotein, which limits its neurological toxicity in humans. Genetic polymorphisms in P-glycoprotein or coadministration of P-glycoprotein inhibitors may increase the neurotoxicity of ivermectin. Other toxic effects of ivermectin after therapeutic oral use include edema, rash, headache, and ocular complaints. Most of these effects are mild and short in duration. Ivermectin exhibits antiviral effects in-vitro at very high concentrations. This has led to suggestions of ivermectin as a potential treatment for SARS-CoV-2 (COVID-19) infection, although the drug's pharmacokinetic parameters reduce the likelihood that high concentrations of the drug can be achieved in-vivo.Conclusion: Due to concern for adverse events, specifically neurotoxicity, as well as a paucity of supporting evidence, the use of ivermectin as a routine treatment or preventive measure for COVID-19 infection is not recommended at this time.

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach.

The SARS-CoV-2 pandemic has accelerated the study of existing drugs. The mixture of homologs called ivermectin (avermectin-B1a [HB1a] + avermectin-B1b [HB1b]) has shown antiviral activity against SARS-CoV-2 in vitro. However, there are few reports on the behavior of each homolog. We investigated the interaction of each homolog with promising targets of interest associated with SARS-CoV-2 infection from a biophysical and computational-chemistry perspective using docking and molecular dynamics. We observed a differential behavior for each homolog, with an affinity of HB1b for viral structures, and of HB1a for host structures considered. The induced disturbances were differential and influenced by the hydrophobicity of each homolog and of the binding pockets. We present the first comparative analysis of the potential theoretical inhibitory effect of both avermectins on biomolecules associated with COVID-19, and suggest that ivermectin through its homologs, has a multiobjective behavior.