Small molecule tubulin inhibitor for COVID-19 treatment

3-[4-(3,4,5-trimethoxybenzoyl)-1H-imidazol-2-yl]-1H-indole (VERU-111)

As discussed in our previous article back in March 2020, it has been shown that coronavirus spike proteins interact with cytoskeleton filaments (i.e. microtubules and actin) for internalization into host cells – a critical step in viral pathogenesis. It has also been shown for some coronaviruses that targeting the cytoskeleton with tubulin or actin inhibitors reduces viral load.

A small molecule tubulin inhibitor, VERU-111 from Veru Inc. has entered Phase 2 study for treatment of COVID-19 patients. As a microtubule depolymerizing agent, VERU-111 is expected to act as an antiviral and anti-inflammatory agent during treatment of SARS-CoV-2.

Veru-111 binds to tubulin at the colchicine binding site and inhibits tubulin polymerization. It disrupts the microtubule filaments similar to some antiviral and anti-inflammatory drugs. As an antiviral, it may have direct effects on SARS-CoV-2’s S protein-microtubule trafficking with the potential to reduce the production of infectious virions particularly by affecting viral replication and assembly and virion egress. As an anti-inflammatory agent, it may reduce virally induced severe inflammation in the respiratory system and may reduce the incidence of cytokine storm and septic shock that can occur in patients that progress to severe acute respiratory pneumonia.

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