Combined administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity

Cholera is a dreadful disease. The scourge of this deadly disease is still evident in the developing world. Though several therapeutic strategies are in practice to combat and contain the disease, there is still a need for new drugs to control the disease safely and effectively. Keeping in view the concern, we screened a small molecule library against a yeast model of cholera toxin A subunit. Our effort resulted in the discovery of a small molecule, apomorphine effective in reducing the lethality of toxic subunit in yeast model. In addition, novobiocin, an inhibitor of ADP ribosylation process, a key biochemical event through which cholera toxin exerts its action on host, was also found to rescue yeast cells from cholera toxin A subunit mediated toxicity. Finally, both molecules prevented cholera toxin mediated cellular toxicity on HT29 intestinal epithelial cells. We also observed that combined administration of both drug molecules worked better than single drug in countering toxin driven lethality.