Introduction
Ivermectin (IVM), a macrocyclic lactone, is a commercially available anti-parasitic drug which prevents infection by a wide range of endo- and ectoparasites (Sajid et al, 2006; Heidary & Gharebaghi, 2020). IVM is an efficient positive allosteric modulator of the α-7 nicotinic acetylcholine receptor (nAChR) (Krause et al, 1998) and of several ligand-gated ion channels, including the muscle receptor for glutamate (GluCl) in worms (Hibbs & Gouaux, 2011). Furthermore, IVM has been shown to exert an immunomodulatory effect in humans and animals (Sajid et al, 2006; Heidary & Gharebaghi, 2020) under conditions that are known to involve the α-7 nAChR (Pavlov & Tracey, 2012), even though its underlying mechanisms are yet to be established (Laing et al, 2017). A direct or indirect interaction of SARS-CoV-2 with nAChR has also been hypothesized, in particular because of sequence homologies between SARS-CoV-2 spike proteins and nAChR ligands such as snake venom toxins (Changeux et al, 2020). IVM has been shown to be active beyond its anti-parasitic activity in a wide variety of pathologies, including cancer, allergy, and viral infections (Laing et al, 2017). Recently, IVM has been reported to reduce viral load and improve the clinical status of mice infected by an animal coronavirus, the mouse hepatitis virus (MHV) (Arévalo et al, 2021). In vitro inhibition of SARS-CoV-2 replication by IVM in Vero/hSLAM cells has also been reported (Caly et al, 2020), albeit at much higher concentrations (50- to 100-fold) than those clinically attainable in humans (150–400 µg/kg) (Guzzo et al, 2002; Bray et al, 2020; Chaccour et al, 2020).
