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Opossum Peptides Could Provide Promising Antivenom

ACS Meeting News: Researchers engineer E. coli to create potent, inexpensive snakebite fighter

by Matt Davenport
March 26, 2015 | A version of this story appeared in Volume 93, Issue 13

A simple peptide could save countless future snakebite victims in developing countries, researchers announced last week at the American Chemical Society national meeting in Denver. The antivenom relies on a sequence of just 11 amino acids, copied from an opossum protein.

Credit: Shutterstock
An opossum.
Credit: Shutterstock

The research team, led by Claire F. Komives of San Jose State University, also demonstrated that genetically modified bacteria could produce the protective peptide at low costs.

Credit: Shutterstock
The Russell’s viper is a common venomous snake in India.
Russell’s viper.
Credit: Shutterstock
The Russell’s viper is a common venomous snake in India.

Komives unveiled the antivenom candidate in a Division of Biochemical Technology session. But the fundamental discoveries behind the findings were made nearly 20 years ago by a researcher named Binie V. Lipps.

Opossums have an innate immunity to a variety of snake venoms. Lipps isolated the protein responsible for this immunity and found that peptides containing its first 10 or 15 amino acids seemed to contain all of the protein’s antivenomous properties. She first patented the work in 1996.

It was widely ignored until 2012, when online news outlets stumbled on the opossum protein thanks to a blogger writing about the remarkable survival ability of opossums. Komives learned about the protein from Yahoo! News while searching for ideas for a research project that would allow her to work with a colleague in India while on sabbatical.

Although deaths from snakebites are rare in the U.S., they are surprisingly common in India. According to some estimates, snakes are responsible for 100,000 deaths in the country every year, Komives said, and people in rural areas, where snakebites are most common, don’t always have access to antivenoms.

Komives decided to try to develop a more inexpensive method for producing the natural opossum product. She was awarded a Fulbright scholarship to pursue the work in October of 2014.

Working with collaborators at the Indian Institute of Technology, Delhi, Komives engineered Escherichia coli to synthesize peptides containing multiple repeats of the first 11 amino acids of the opossum protein. The researchers then use a protease to cleave at the final amino acid in that sequence to release the individual peptides.

Producing the peptides required simply ordering a plasmid and growing engineered bacteria, Komives said, but the team does need to optimize the peptide purification process. She estimates that once scaled up, companies could produce the peptides at roughly $1.00 per g.

Meanwhile, collaborators at the National Natural Toxins Research Center at Texas A&M University, Kingsville, have confirmed that synthetic versions of the 11-mer peptide protect mice against the hemorrhagic effects of venom from Russell’s viper (Daboia russelii), a common snake in India, and help mice survive exposure to rattlesnake venom.

Michael G. Thomas, a bacteriologist at the University of Wisconsin, Madison, and a chair of the session in Denver, said he was impressed by how much of an impact this simple peptide could make.

“The bottom line is the peptide clearly does something,” said Komives, who is working to establish a crowdsourcing campaign to better understand its efficacy. “Somebody needs to be working on this.”


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