Hospitals are using antibiotics as a last resort to fight infections. But with the rapid spread of diseases like Ebola and Zika, the healthcare and science community is challenged with developing new antimicrobials to protect people from these diseases.

ASU scientists have recently met a challenge of developing a new class of antimicrobials, called synbodies, to safeguard the population against infectious threats -- all within a week. Source: Biodesign Institute, Arizona State University

The research division of the U.S. Department of Defense, the Defense Advanced Research Program Agency, or DARPA, is known for taking on challenges larger than this one. Because of this, they challenged researchers to figure out how to make at least 1,000 doses of any known pathogen in a week.

The Arizona State University (ASU) team was one of only a few that took on this challenge and completed it successfully.

"As far as we know we were the only team to figure out how to do this for any pathogen — virus or bacterium," said research leader Stephen Albert Johnston, who directs the ASU Biodesign Institute's Center for Innovations in Medicine and is a professor in the School of Life Sciences. "While the system is designed to create antimicrobials in an extreme emergency — which we hope is never needed — the basic elements can be applied to improve conventional approaches to making anti-infective."

To make an antibody in a lab can take months and is often an expensive endeavor. Johnston wanted to mimic nature’s approach and dramatically reduce the antimicrobial discovery and production time.

For over a decade, Johnson’s team has been pioneering the development of lab-made versions that focus on only the business end of antibodies: critical pathogen recognition elements called synthetic antibodies, also known as synbodies. Synbodies are made to form two short protein fragments, called peptides, which are joined together to form a small, antibody-like compound that is still large enough to get the job done.

Even the process of making synbodies can take several months. Synbodies are selected on peptide chips containing a pre-made set of 10,000 peptides placed in neat rows on a microarray, a microscope glass slide. In order to generate a synbody with antibiotic activity, a solution containing bacteria or viruses can be placed on the microarray.

"Our solution to save time was to pre-screen a large number of pathogens on the microarray and find 100 peptides that would be diverse enough so that any pathogen screened would bind to two or more peptides," said Chris Diehnelt, an associate research professor in Johnston's center who oversaw the lab experiments.

Researchers could stockpile around 100 peptides in advance so that 1,000 or more doses of a therapeutic agent could be quickly produced through screening the best candidates that block a given pathogen. These candidates are then produced in large amounts, purified and tested in mice for acute toxicity. The process can be completed entirely in a week.

The team screened a total of 21 different viruses and bacteria against synbody arrays. They also tested their system against two unknown pathogens that were not used in a study.

"The data showed that this array can potentially identify binding peptides for any given pathogen," said Diehnelt.

The best candidates for this research were quickly evaluated for effective killing and toxicity to humans while also being able to be produced on a large scale. Their system was tested against two societal scourges and major worldwide health concerns: a flu strain (H1N1 influenza) was used as a viral test and a bacterium that causes surgery-related infections called S. epidermidis.

"Our data indicate that a new virus or bacterium can be screened against the small peptide library to discover binding peptides that can be converted into neutralizing antiviral and antibacterial synbodies in a rapid manner," said Diehnelt.

The next step for the team is to prepare the final product for an IV delivery and to scale up the system to produce enough product to be used worldwide for the next disease breakout.

"One key, unique feature of our synbody technology is that the same platform can produce synbodies with direct antibiotic or antiviral activity, and we can do it at a fraction of the potential cost as current, commercially produced therapeutic antibodies," said Johnston.

This could mean big business for Johnston as far as the potential to save thousands of lives. The global therapeutic monoclonal antibody market and cancer therapies are currently in high demand with an estimated market size close to $100 billion in 2018.

A paper on this research was published in Scientific Reports.