Protein that could Improve Symptoms and Reduce Mortality in Flu

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Structural characterization of retrocyclin. (a) CD spectrum demonstrating the similarity in structure between retrocyclin and RTD-1, both at 0.5 mg/ml in a 1:1 mixture of trifluoroethanol in PBS at pH 7.4. (b) A hypothetical model of retrocyclin made by templating its sequence on the backbone of a similar peptide from porcine neutrophils, protegrin-1 (PDB accession code: 1PG1). (c) A cartoon version of b, wherein arginines are black, cysteines are gray, and the other residues are identified by single letter code. (d) A similar cartoon of rhesus RTD-1, indicating the similarity in structure with retrocyclin.

Structural characterization of retrocyclin. (a) CD spectrum demonstrating the similarity in structure between retrocyclin and RTD-1, both at 0.5 mg/ml in a 1:1 mixture of trifluoroethanol in PBS at pH 7.4. (b) A hypothetical model of retrocyclin made by templating its sequence on the backbone of a similar peptide from porcine neutrophils, protegrin-1 (PDB accession code: 1PG1). (c) A cartoon version of b, wherein arginines are black, cysteines are gray, and the other residues are identified by single letter code. (d) A similar cartoon of rhesus RTD-1, indicating the similarity in structure with retrocyclin.

New research in the Journal of Leukocyte Biology identifies potential protective agent against flu infection. Scientists showed that a small protein called retrocyclin-101 (RC-101) could potentially improve the symptoms and mortality associated with the flu and possibly other types of infectious illness. As a potential drug candidate, RC-101 is unique in that it not only targets the influenza virus, but also the harmful inflammation it causes.

“Every year, thousands of people across the country die from the flu or its complications – despite widespread use of annual influenza vaccines,” said Daniel J. Prantner, PhD, a research associate in the Department of Microbiology and Immunology at the University of Maryland School of Medicine (UM SOM). “In the future, we hope to see RC-101 approved for use in the clinic, where it can be another tool in the battle against this disease.”

To make their discovery, Dr. Prantner and his colleagues used isolated mouse and human macrophages in vitro, and a mouse influenza infection model. Using the isolated macrophage model, the researchers found that RC-101 inhibited the production of inflammatory cytokines. In the animal model, the researchers infected two groups of mice with a lethal dose of influenza. They gave one of these groups RC-101 two days after infection for a total of five days, and gave the other group a placebo control. The mice that were treated with RC-101 exhibited less severe symptoms of the flu and decreased mortality compared to the control group.

“While viruses such as influenza cause a lot of damage themselves when people get infected, it is often the immune response that leads to severe tissue destruction trying to eradicate the infection,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “These new findings using RC-101 may teach us how to efficiently allow the immune response clears a virus, while preventing the most damaging parts of the inflammatory response.”

https://eurekalert.org/pub_releases/2017-09/foas-nsi092917.php

http://www.jleukbio.org/content/102/4/1103.abstract