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Using caffeine to ward off disease

Researchers create new antibody-like molecules that can control human biological processes and potentially neutralize SARS-CoV-2, the coronavirus that causes COVID-19

About 65 percent of American adults drink coffee daily. Coffee can give a person a boost of energy in the morning, and some studies show that coffee may have the potential to improve a person’s health by reducing the risk of diabetes and dementia. Coffee can make people feel less tired and revitalize energy levels because it contains a key stimulant: caffeine, the most widely consumed psychoactive substance in the world.

Researchers from the laboratories of Yubin Zhou, MD, PhD, and Yun Nancy Huang, MD, PhD, located at the Texas A&M Institute of Biosciences and Technology and Department of Translational Medical Science at the Texas A&M University College of Medicine, are trying to harness caffeine’s power to control biological processes from cancer to infectious disease—even potentially the novel coronavirus that causes COVID-19. They developed a genetically encoded “caffeine-operated synthetic module,” or “COSMO.” COSMO allows scientists to precisely and reversibly control protein activity and physiological processes of humans by using caffeine and its metabolites, such as theobromine, which is also abundantly present in cocoa and chocolate. These findings were published as a cover article in the journal Advanced Science.

The researchers have shown that COSMO is very sensitive to caffeine or theobromine. They found that a cup of Starbucks Caffè Americano, a can of soda or even a dark chocolate bar consumed by an adult would be enough to activate biological processes controlled by COSMO.

“The invention is based on an anti-caffeine nanobody, a minimal antigen-recognition fragment derived from llamas, that undergoes a change, called ‘dimerization,’ upon binding with caffeine,” said Zhou, an associate professor and American Cancer Society Research Scholar at Texas A&M University who spearheaded the study.

Tianlu Wang, PhD, and Lian He, PhD, postdoctoral research associates and the two lead authors of the study, developed a high throughput cellular assay—a method which enabled them to rapidly test hundreds of samples of biological activity at the cellular level—to identify a nanobody that can engage caffeine. They found that the nanobody is one of the most potent chemically inducible dimerization systems that could benefit both basic and translational research.

“The COSMO system is amazingly powerful since it enables us to control calcium flux into cells and efficiently induce cancer cell death within seconds or minutes,” said Guolin Ma, PhD, assistant research professor from the Zhou group who also supervised the study. “We could also use caffeine to bypass the need for growth factors to activate cell signaling cascades and to remodel the cytoskeleton of a human cell.”

Combining the COSMO with the nanobody could also potentially neutralize SARS-CoV-2, the virus that causes COVID-19. The team discovered that caffeine-inducible homodimerization, the process of joining two identical molecule subunits to form a whole complex, of these nanobodies could substantially increase COSMOS’s ability to engage invading viruses.

“This means that our novel strategy promises to be more effective in neutralizing the virus infectivity than using nanobodies alone,” Wang said. “We hope that our findings can advance the development of more potent and smart biologics against COVID-19 to some extent.”

In the future, the researchers hope that COSMO can be engineered into proteins in order to effectively take complete control of therapeutic cells and biological processes of caffeine and its metabolites.

“Try to imagine that you have one cup of regular coffee or some bites of chocolate in the morning,” said Huang, a Cancer Prevention and Research Institute of Texas Scholar and associate professor. “Caffeine-‘addicted’ therapeutics in your body will start to work against pathogens and cancer. This is the bold idea that we are pursuing in future studies.”

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