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Cholera is an acute gastrointestinal disease that produces rapid dehydration and affects millions of people around the globe, mostly children.

This threat has been made even more dire in recent decades, as the gastrointestinal disease—caused by the bacterium Vibrio cholerae—has grown increasingly resistant to antibiotics.

“In a recent study in sub-Saharan Africa and many other places cholera is prevalent, it is shown that 100 percent of the clinical samples they have are resistant to multiple antibiotics,” says 91��Ƭ�� Tech Associate Professor of Biology Oscar Juarez. The impact of this disease was evident in Haiti, where a cholera outbreak produced a collapse of the health care system in the country.

Juarez and his team at 91��Ƭ�� Tech—Ph.D. students Ming Yuan (Ph.D. MBB ’24) and Yuyao Hu (Ph.D. BIOL Candidate ), postdoc Martin Andres Gonzalez Montalvo, and Assistant Professor of Biology Karina Tuz—h������ , demonstrating that it is effective to combat multi drug-resistant strains of cholera.

Previously, clofazimine had been used to treat leprosy and tuberculosis. The drug’s manufacturer, however, discontinued production for the United States nearly a decade ago.

Juarez’s lab focused on understanding how cholera survives in the human body, identifying a protein called NQR that plays a central role in the disease’s ability to produce energy.

Clofazimine works by inhibiting NQR, which cuts off the bacteria’s energy supply and, ultimately, would destroy the infection.

“Our study shows that NQR is super important for Vibrio cholerae to produce energy. We identified where exactly it is that clofazimine binds to,” says Juarez, adding: “The cell has thousands of different proteins. What we did was identify the target of clofazimine in Vibrio cholerae, which is NQR.”

Unlike typical drug discovery efforts—which often involve testing thousands of molecules—Juarez’s team already knew which type of molecule with inhibitory properties that it was looking for. Because of this prior knowledge, the team only had to test around 20 molecules instead of the typical hundreds of thousands.

“What we’re doing is actually engineering drug design, because we know the properties of molecules that should have inhibitory effects over NQR and over Vibrio cholerae,” says Juarez. “We have enough information to be able to predict the type of molecules that have inhibitory properties and to speed up drug discovery and drug design.”

The next step in repurposing clofazimine to treat cholera most effectively will involve modifying it—specifically, grouping chemicals in different positions in order to make it a better inhibitor.

It’s a process Juarez playfully refers to as molecular Tetris.

“When you’re playing Tetris, you’re making something fit in a specific position,” says Juarez. “What we’re doing is taking the structure of clofazimine—which fits well into the pocket of a protein—and if we include another chemical group that makes it fit better, then it will be more potent.”

The biggest perk of repurposing an already-known drug? Clofazimine is already approved by the U.S. Food and Drug Administration, which saves years and billions of dollars of trials and research.

“The approval requires about $2.1 billion and about 10 years of testing,” says Juarez. “The three levels of clinical trials in humans, we may skip them, because we already know clofazimine is safe.”

As a result, a safe, effective treatment for multi drug-resistant cholera could be just around the corner, at the cost of around $20 per dose. Juarez and his team are in the process of patenting the use of clofazimine to treat cholera.

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