4.13. Levamisole
It is a tetrahydro-imidazothiazole derivative (Figure S6) that has been used for its immunomodulatory properties. It was first introduced by Janssen in 1969. Ever since, it was used as a disease-modifying drug for the treatment of rheumatoid arthritis [222,223,224]. It was also used with 5-fluorouracil for colon cancer treatment [225]. Currently, it is primarily used as an anthelmintic agent for the treatment of ascariasis and hookworm infections owing to its effect on the parasitic nicotinic acetylcholine receptors [226]. It is also used by pediatric nephrologists as a steroid-sparing agent in childhood steroid-dependent nephrotic syndrome [227].
A recent computational exercise has suggested that levamisole potentially binds to the catalytic domain of the viral PLpro, a viral enzyme that processes the newly biosynthesized viral polyproteins and eventually contributes to the maturation and infectivity of the virus [228]. Yet, no experimental validation has been reported thus far. As of now, orally administered levamisole is being studied alone or in combination with budesonide/formoterol inhaler for the treatment of COVID-19 in few clinical trials. The rationale for this use has been because of its immunomodulatory effects. Levamisole acts as an immune-modulator and immune-enhancer by increasing T-cell lymphocyte function and macrophage chemotaxis. It has also been shown to up-regulate toll-like receptors, stimulate neutrophil chemotaxis, and enhance dendritic cell maturation [229,230]. Furthermore, levamisole attenuated alveolar macrophage dysfunction in respiratory virus-infected calves [231].