Sabizabulin is an orally bioavailable bis-indole that binds to the “colchicine binding site” of a and b tubulin and inhibits tubulin polymerization at low nanomolar concentrations. Sabizabulin disrupts the microtubule filaments similar to nocodazole and colchicine, the central mechanism that contributes to both their antiviral and anti-inflammatory activities.
…The central mechanism of colchicine clinical anti-inflammatory and anti-viral activities is based on its ability to bind the “colchicine binding” sites on alpha and beta tubulin which when incorporated into microtubule block subsequent microtubule polymerization. Inhibition of tubulin polymerization is responsible for the effects of colchicine on cell migration, cytokine release, and intracellular trafficking (antiviral) and disruption of inflammatory cell activities…
Colchicine modulates leucocyte mediated inflammatory activities including inhibition of leucocyte production of superoxides and release of various cytokines and pyrogens. Colchicine-like agents may therefore be useful in treating the “cytokine storm” seen with SARS-CoV-2.
So, according to the company, sabizabulin has a dual anti-inflammatory/antiviral MoA, but I question whether the antiviral MoA is a material contributor to efficacy in already hospitalized patients with severe COVID.
p.s. Colchicine is the standard second-line agent (following NSAIDs) for pericarditis.
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